Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records
Reference
Endpoint:
one-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data available from study report.
Qualifier:
according to
Guideline:
other: Data is from Journal with permission
Principles of method if other than guideline:
Reproductive toxicity study of D&C Yellow No. 11 orally in rat orally
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:

Source: Taconic Farms (Germantown, NY)
- Age at study initiation: (P) Thirty-two-day-old male and female(F0)
-(F1) x wks: No data 42 days
- Age at study initiation: (P) 112 days old
- Weight at study initiation: (P) No data available
- Fasting period before study: No details available
- Housing: Rats were housed five per cage
Animals were housed in Solid-bottom polycarbonate changed twice weekly except from day 18 of gestation through delivery. Animals were bedded on Sani-Chips changed twice weekly except from day 18 of gestation through delivery. Reemay® spun-bonded polyester Rack Filters changed once every 2 weeks except from day 18 of gestation through delivery Stainless steel changed once every 2 weeks except from day 18 of gestation through delivery. Identified by Tail tattoo. Animals were housed 5 per cage before cohabitation, 1 pair during cohabitation and 5 males or 1 dam and litter aafter cohabitation.
- Use of restrainers for preventing ingestion (if dermal): No details
- Diet : NIH-07 open formula mash ad libitum
Water: : Tap water via automatic watering system, ad libitum
- Acclimation period: Animals were quarantined for 10 Days

ENVIRONMENTAL CONDITIONS
Temperature (°C): 20.0-25.6’c
Humidity :23.3% to 81.2%
- Air changes (per hr): minimum of 10 changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours/day

IN-LIFE DATES:
From: 18 December 1989

To: male: 13 March 1990
Female: 24 april 1990
Route of administration:
oral: feed
Type of inhalation exposure (if applicable):
not specified
Vehicle:
other: NIH-07 open formula mash
Details on exposure:
Details on exposure
PREPARATION OF DOSING SOLUTIONS: Dose were prepared by mixing D&C Yellow No. 11 in the concentration of 0, 500, 1,700, and 5,000 ppm with NIH-07 open formula mash feed. D&C Yellow No. 11/feed premix was made by hand and then blended with feed in a Patterson-Kelly twin-shell blender for 15 minutes with the intensifier bar on for the first 5 minutes.
- Rate of preparation of diet (frequency): every 2 weeks
- Mixing appropriate amounts with (Type of food):The dose formulations were prepared every 2 weeks by mixing D&C Yellow No. 11 with feed (Table G1). A D&C Yellow No. 11/feed premix was made by hand and then blended with feed in a Patterson-Kelly twin-shell blender for 15 minutes with the intensifier bar on for the first 5 minutes. 0, 500, 1,700, and 5,000 ppm in NIH-07 open formula mash feed.
- Storage temperature of food:During the studies, dose formulations were stored in double-thickness plastic bags in rigid plastic containers at room temperature protected from light for up to 3 weeks.
VEHICLE
- Justification for use and choice of vehicle (if other than water): NIH-07 open formula mash feed
- Concentration in vehicle: 0, 500, 1,700, and 5,000 ppm
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Details on mating procedure:
- M/F ratio per cage: During cohabitation -one male and one female per cage
- Length of cohabitation: 7 days
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy
During cohabitation, vaginal smears were taken daily from females to determine the presence of sperm.
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. No data
- Further matings after two unsuccessful attempts: [no / yes (explain)] No data
- After successful mating each pregnant female was caged (how): 1 dam per cage
- Any other deviations from standard protocol:
Analytical verification of doses Yes

Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Homogeneity and stability studies of the 500 ppm dose formulation were performed by the analytical chemistry laboratory using high-performance liquid chromatography. Homogeneity was confirmed and the stability of the dose formulations was confirmed for at least 3 weeks when stored protected from light at room temperature and for 7 days when stored open to air and light. Periodic analyses of the dose formulations of D& C Yellow No. 11 were ferpormed by using visible spectrometry. During the reproductive study the formulations wer e analyzed approximately every 8 weeks.
Duration of treatment / exposure:
Total: 125 weeks
Male: 13 weeks
Female: 19 weeks
F1: 106 week
Frequency of treatment:
Daily
Details on study schedule:
First-generation (F0 ) rats started on D&C Yellow No. 11 in feed---->70-day precohabitation period---->7-day cohabitation period---->21-day gestation period---->28-day lactation period---->Second-generation (F1 ) rats continued on same concentrations of D&C Yellow No. 11 in feed as dams for 2 years---->Terminal sacrifice
Remarks:
Doses / Concentrations:
0, 500, 1,700 and 5,000 ppm (0, 35, 120 and 350 ma/kg body weight /day for male and 0, 35, 120 and 370 ma/kg body weight /day for female )
Basis:
nominal in diet
No. of animals per sex per dose:
Total: 480
0 ppm : 60 male, 60 female
25 ppm : 60 male, 60 female
85 ppm : 60 male, 60 female
250 ppm : 60 male, 60 female
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: The results of the 13-week rat study were used to select doses of 500, 1,700, and 5,000 ppm for the current F344/N rat study. In the 13-week feed study, rats were given 500, 1,700, 5,000, 17,000 and 50,000 ppm. There was no perinatal exposure, and animals were about 6 weeks old when placed on dosed feed. Mean body weights of males and females were significantly reduced after 13 weeks of exposure to 17,000 and 50,000 ppm, and there was mild hepatocellular periportal degeneration in 7 males given 17,000 ppm, in all 10 given 50,000 ppm, and in 2 females given 50,000 ppm. This lesion was minimal at doses of 1,700 and 5,000 ppm in males (4/4, 9/10) and females (2/2, 7/7) and in females at 17,000 ppm (9/10) and was not observed in groups given 500 ppm. In addition, a range-finding study was conducted in which female rats were given 5,000, 17,000, or 50,000 ppm D&C Yellow No. 11 in feed for 4 weeks before mating and during mating, gestation, and the first 4 weeks after having litters. Pups were weaned at week 4 and continued on the same feed as their dams for an additional 4 weeks. Litters would have been potentially exposed in utero, through lactation, and feed. There was no difference between study groups in reproductive performance. However, pup body weights in the 17,000 and 50,000 ppm groups were decreased at 8 weeks of age. Microscopic evaluation showed that the liver lesions in exposed pups were similar to those described for the 13-week study.

- Rationale for animal assignment (if not random): Rats were distributed randomly into groups of approximately equal initial mean body weights.

- Other: No data available
Positive control:
No data
Parental animals: Observations and examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
- Cage side observations checked in table [No.?] were included: Mortality were observed.

DETAILED CLINICAL OBSERVATIONS: Yes clinical findings on day one and weekly before cohabitation for F0 Males and Females And on day 0, 6, 15 and 21of gestation for females & on days 1, 4, 14, and 21 of lactation for F females and F1 pups.

BODY WEIGHT: Yes on day one and weekly before cohabitation for F0 Males and Females And on day 0, 6, 15 and 21of gestation for females & on days 1, 4, 14, and 21 of lactation for F females and F1 pups.

Feed consumption was recorded by cage weekly before cohabitation, ondays 0, 6, 15, and 21 during gestation, and on days 1, 4, 14, and 21 during lactation.

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
Oestrous cyclicity (parental animals):
Any irregularities in the estrous cycle were investigated.
Sperm parameters (parental animals):
No data available
Litter observations:
Survival, clinical sign, number and sex of pups, body weight, feed consumption were examined.
Postmortem examinations (parental animals):
HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated were prepared for microscopic examination and weighed, respectively-Yes
Postmortem examinations (offspring):
Hematology, Organs weighed and histopathology were examined.
Statistics:
Body weight data for F rats, maternal body weight data during gestation and lactation, litter weight data, pup delivery data, percent male pups, and pups surviving on days 4 and 21 were analyzed by using Williams’ or Dunnett’s test. Feed consumption data for F0 rats were analyzed by using Dunn’s or Shirley’s test.
Reproductive indices:
Fertility index and implantation sites were examined.
Offspring viability indices:
Viability on day 4 were observed
Clinical signs:
effects observed, treatment-related
Body weight and weight changes:
effects observed, treatment-related
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Other effects:
effects observed, treatment-related
Description (incidence and severity):
Test substance intake: Dietary levels of 500, 1,700, and 5,000 ppm D&C Yellow No. 11 resulted in average daily doses of approximately 35, 120, and 350 mg /kg body weight for males and 35, 120, and 370 mg/kg for females.
Reproductive function: oestrous cycle:
no effects observed
Description (incidence and severity):
No effect were observed on Reproductive function of treated rat as compared to control.
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
No effect were observed on Reproductive performance of treated rat as compared to control.
Clinical signs:
Mortlity:
No effect were observed on survival of treated rat as compared to control.
Clinical signs:
Yellow discoloration of the entire body or fur in all males and females observed at 1,700 and 5,000 ppm dose and in all males and seven females at 500 ppm dose .
In all rats at 1,700 and 5,000 pp m, urine-stained abdominal fur were observed.
Yellow discoloration of the fur was observed in all exposed female rats during gestation and lactation as compared to control.


Body weight and food consumption:
Prior to cohabitation, mean body weight gains of males (days 1 to 71) at 500, 1,700 and 5,000 ppm and of females (days 1 to 66) at 5,000 ppm were significantly decreased as compared to controls.
The mean body weight gains of exposed females during gestation and lactation were generally similar to those of the controls
Dose descriptor:
NOAEL
Effect level:
35 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effect on survival, clinical sign, body weight and body weight gain, food consumption and compound intake
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Clinical signs:
effects observed, treatment-related
Mortality / viability:
not specified
Body weight and weight changes:
effects observed, treatment-related
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
Significant increase in absolute and relative liver weights were observed in all the treated pups as compared to control.
Gross pathological findings:
effects observed, treatment-related
Histopathological findings:
effects observed, treatment-related
Clinical signs:
Mortlity:
When treated with 1700 and 5000 ppm , significant decrease were observed in survival of male pups and at 5000 ppm in female as compared to control.
Clinical signs:
Yellow discoloration of the entire body in all exposed male and female pups from day 1 and head swelling and edema in 1,700 and 5,000 ppm males pups were observed as compared to control.

Body weight:
The mean body weights of exposed pups were significantly less than those of the control litters on days 14 and 21 in 1700 and 5000 ppm dose group.
Food consumption:
No effect was observed on food consumption of treated pups as compared to control.

Test substance intake:
Dietar y levels of 500, 1,700, and 5,000 ppm D&C Yellow No. 11 resulted in average daily doses of approximately 25, 85, and 250 mg /kg body weight for males and 25, 100, and 280 mg/kg body weight for females.

Gross pathology:
Renal tubule adenomas, Hepatocellular adenoma in 1700 and 5,000 ppm treated males pups and Renal tubule adenomas, hepatocellular adenoma or carcinoma (combined) in 1700 and 5,000 ppm treated females pups were observed as compared to control.
Squamous cell carcinomas of the tongue were observed in one 500 ppm male pup at 12 months and one 5,000 ppm female pup at 2 years were observed.
Renal tubule pigmentation were observed in all the treated male and female pups as compared to control.
Squamous cell papillomas were observed in the oral cavity (oral mucosa or tongue) of 1700 and 15000 ppm treate male pups.

Histopathology:
Mixed cell foci and clear cell foci in 1700 and 5000 ppm treated male and female pups were observed.
Cytologic alterations (basophilia and granularity) o f hepatocytes, and pigmentation in bile duct epithelium, hepatocytes, and Kupffer cells in treated male and female pups were observed.
Necrosis and regeneration of the renal tubule epithelium were observed in all the treated male and female pups.
Hyperplasia of the transitional epithelium in the kidney of 1700 ppm treated male and female pups.

other findings:
Hematology:
Minimal anemia in all the treated males were observed ; this anemia was characterized by decreased hematocrit values, hemoglobin concentra tions, and erythrocyte counts.
Th e minimal anemia was characterized as normocytic , normochromic, and nonresponsive. Normocytic , normochromic, nonresponsive anemias have been related to selective suppression of erythropoiesis in a variety of disorders and may be due to decreased erythropoietin elaboration, bone marrow suppression, or defective iron metabolism.
Therefore, the observed effect is not biologically or statistically significant than control.
Dose descriptor:
LOAEL
Generation:
F1
Effect level:
25 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Effect on organ weight, gross pathology and histopathology
Remarks on result:
other: not specified
Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified
Conclusions:
The no observed adverse effect level (NOAEL) for F0 generation was considered to be 500 ppm (35 mg/kg body weight /day) and The Low observed adverse effect level (LOAEL) LOAEL for F1 generation was considered to be 500 ppm (25 mg/kg body weight /day) when F344/N male and female rats were treated with D&C Yellow No. 11.
Executive summary:

 In a reproductive toxicity study,F344/N male and female rats were treated with D&C Yellow No. 11. in the concentration of0, 500, 1,700 and 5,000 ppmorally in diet.Yellow discoloration of the entire body or fur and urine-stained abdominal fur. Significantly decreased in mean body weight gains ofF0males were observed at 500, 1,700 and 5,000 ppm. The mean body weights of exposed litters were significantly less than those of the control litters on days 14 and 21 in 1700 and 5000 ppm dose.In F1 generation, effect were observed as significant decreasein survival,Yellow discoloration of the entire bodyof pups, head swelling and edema in 1,700 and 5,000 ppm males pupsand Significant increase in absolute and relative liver weights were observed in all the treated pups as compared to control. In addition, Renal tubule adenomas, Hepatocellular adenoma in 1700 and 5,000 ppm treated males pups and Renal tubule adenomas, hepatocellular adenoma or carcinoma (combined) in 1700 and 5,000 ppm treated females pups, Squamous cell carcinomas of the tongue were observed in one 500 ppm male pup at 12 months and one 5,000 ppm female pup at 2 years, Renal tubule pigmentation in all the treated pups and Squamous cell papillomas of oral cavity (oral mucosa or tongue) in 1700 and 15000 ppm treated male pups were observed. Histopathological changes such as Mixed cell foci and clear cell foci in 1700 and 5000 ppm, Cytologic alterations (basophilia and granularity) o f hepatocytes, and pigmentation in bile duct epithelium, hepatocytes, and Kupffer cells in treated male and female pups, Necrosis and regeneration of the renal tubule epithelium in all the treated male and female pups and Hyperplasia of the transitional epithelium in the kidney of 1700 ppm treated male and female pups were observed as compared to control. Therefore,NOAEL for F0 generation was considered to be 500 ppm (35 mg/kg body weight /day) and LOAEL for F1 generation was considered to be 500 ppm (25 mg/kg body weight /day) when F344/N male and female rats were treated with D&C Yellow No. 11. Orally in diet for125 weeks.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
35 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
K2 level data .
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

WoE Summary of 8003-22-3 for toxicity to reproduction

Based on the various studies available with Klimish rating 2 and predicted data for the target substances CAS: 8003-22-3 the results is summarized as follows:

Sr. No

End point

Value

Species

Effects

Remarks

1

NOAEL

35 mg/kg bw/day (nominal)

(P generation)

Rat

(male & female)

No adverse effect on survival, clinical sign, body weight and body weight gain, food consumption and compound intake

Data from study report for 8003-22-3

2

LOAEL

25 mg/kg bw/day (nominal)

(F1 generation)

Rat

(male & female)

Effect on organ weight, gross pathology and histopathology

Data from study report for 8003-22-3

3

NOEL

85 mg/kg bw/day (nominal)

(F1 generation)

Rat

(female)

All the serological test results were negative for reproductive toxicity.

Data from study report for 8003-22-3

4

LOAEL

85 mg/kg bw/day (nominal)

(F1 generation)

Rat

(male)

All the serological test results were negative for reproductive toxicity.

Data from study report for 8003-22-3

5

NOAEL

829 mg/kg bw/day (actual dose received)

Rat

No effect observed on organ weight

Data from Publication for 8003-22-3

6

NOEL

751 mg/kg bw/day (actual dose received)

Rat

No effect observed on organ weight

Data from Publication for 8003-22-3

 

Based on the studies summarized in the above table it can be observed that, the no observed adverse effect level (NOAEL) value found to be 35 mg/kg bw/day (nominal). While from predicted data NOAEL values predicted as 829 mg/kg bw/day (actual dose received). Also the NOEL value found to be 85 mg/kg bw/day (nominal). While from predicted data values predicted as 751 mg/kg bw/day (actual dose received).

In F1 generationthe Low observed adverse effect level (LOAEL) values found to be 25 mg/kg bw/day (nominal) and 85 mg/kg bw/day (nominal)

All the serological test results were negative for reproductive toxicity in the 35 mg/kg/day group in parent generation.

Thus based on above discussion it can be concluded that substance CAS: 8003-22-3 is considered to be not toxic to reproduction at the above mentioned dose.

Short description of key information:

The no observed adverse effect level (NOAEL) for F0 generation was considered to be 500 ppm (35 mg/kg body weight /day) and The Low observed adverse effect level (LOAEL)  LOAEL for F1 generation was considered to be 500 ppm (25 mg/kg body weight /day) when  F344/N male and female rats were treated with  D&C Yellow No. 11.

Justification for selection of Effect on fertility via oral route:

Data available from study report.

For the reproductive toxicity study in rats, all serology test results were negative.No significant effects were observed  as compared to control with respect to target chemical.

Effects on developmental toxicity

Description of key information

The developmental toxicity LOEL (Lowest Observed Effect Level) of D&C Yellow No. 11 in Sprague Dawley rat by the oral route was estimated to be 99.1999 mg/kg bw/day.

Link to relevant study records
Reference
Endpoint:
developmental toxicity
Type of information:
(Q)SAR
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data is from QSAR Toolbox Version 3.3
Justification for type of information:
QSAR prediction: migrated from IUCLID 5.6
Qualifier:
according to
Guideline:
other: The prediction is done using QSAR Toolbox version 3.3
Principles of method if other than guideline:
The prediction is done using QSAR Toolbox version 3.3
GLP compliance:
no
Limit test:
yes
Species:
rat
Strain:
other: Sprague Dawley
Route of administration:
oral: gavage
Vehicle:
not specified
Details on exposure:
No Data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No Data
Details on mating procedure:
No Data
Duration of treatment / exposure:
21 days
Frequency of treatment:
Daily
Duration of test:
No Data
No. of animals per sex per dose:
No data available
Details on study design:
No data available
Maternal examinations:
No data available
Ovaries and uterine content:
No data available
Fetal examinations:
No data available
Statistics:
No data available
Indices:
No data available
Historical control data:
No data available
Details on maternal toxic effects:
Maternal toxic effects:no data
Dose descriptor:
other: not specified
Based on:
not specified
Basis for effect level:
other: not specified
Remarks on result:
other: not specified
Abnormalities:
not specified
Localisation:
not specified
Description (incidence and severity):
not specified
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no data
Dose descriptor:
LOEL
Effect level:
99.2 mg/kg bw/day
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: fetotoxicity
Remarks on result:
other: not specified
Abnormalities:
not specified
Localisation:
other: not specified
Description (incidence and severity):
not specified
Developmental effects observed:
not specified
Treatment related:
not specified
Relation to maternal toxicity:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

The prediction was based on dataset comprised from the following descriptors: LOEL
Estimation method: Takes average value from the 5 nearest neighbours
Domain  logical expression:Result: In Domain

((((("a" or "b" or "c" or "d" )  and ("e" and ( not "f") )  )  and (("g" or "h" or "i" or "j" )  and ("k" and ( not "l") )  )  and (("m" or "n" or "o" or "p" )  and ("q" and ( not "r") )  )  )  and ("s" and ( not "t") )  )  and ("u" and "v" )  )

Domain logical expression index: "a"

Referential boundary: The target chemical should be classified as Aryl AND Diketone AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND Indandione AND Pyridine AND Quinoline/ Isoquinoline by Organic Functional groups

Domain logical expression index: "b"

Referential boundary: The target chemical should be classified as Fused carbocyclic aromatic AND Indandione AND Overlapping groups AND Quinoline/ Isoquinoline by Organic Functional groups (nested)

Domain logical expression index: "c"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Carbonyl, aliphatic attach [-C(=O)-] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "d"

Referential boundary: The target chemical should be classified as Aromatic compound AND Carbonyl compound AND Ketone by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "e"

Referential boundary: The target chemical should be classified as No alert found by DNA binding by OECD

Domain logical expression index: "f"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Isocyanates and Isothiocyanates OR Acylation >> Isocyanates and Isothiocyanates >> Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Benzylamines-Acylation OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Formamides OR Acylation >> P450 Mediated Activation to Isocyanates or Isothiocyanates >> Sulfonylureas OR Michael addition OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Furans OR Michael addition >> P450 Mediated Activation of Heterocyclic Ring Systems >> Thiophenes-Michael addition OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Alkyl phenols OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Arenes OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Hydroquinones OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Methylenedioxyphenyl OR Michael addition >> P450 Mediated Activation to Quinones and Quinone-type Chemicals >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated amides OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated esters OR Michael addition >> Polarised Alkenes-Michael addition >> Alpha, beta- unsaturated ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinones OR Schiff base formers OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethanolamines (including morpholine) OR Schiff base formers >> Chemicals Activated by P450 to Glyoxal  >> Ethylenediamines (including piperazine) OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes OR Schiff base formers >> Chemicals Activated by P450 to Mono-aldehydes >> Benzylamines-Schiff base OR Schiff base formers >> Direct Acting Schiff Base Formers OR Schiff base formers >> Direct Acting Schiff Base Formers >> Mono aldehydes OR SN1 OR SN1 >> Carbenium Ion Formation OR SN1 >> Carbenium Ion Formation >> Allyl benzenes OR SN1 >> Carbenium Ion Formation >> Diazoalkanes OR SN1 >> Carbenium Ion Formation >> N-Nitroso (alkylation) OR SN1 >> Carbenium Ion Formation >> Polycyclic (PAHs) and heterocyclic (HACs) aromatic hydrocarbons-SN1 OR SN1 >> Iminium Ion Formation OR SN1 >> Iminium Ion Formation >> Aliphatic tertiary amines OR SN1 >> Nitrenium Ion formation OR SN1 >> Nitrenium Ion formation >> Aromatic azo OR SN1 >> Nitrenium Ion formation >> Aromatic N-hydroxylamines OR SN1 >> Nitrenium Ion formation >> Aromatic nitro OR SN1 >> Nitrenium Ion formation >> Aromatic nitroso OR SN1 >> Nitrenium Ion formation >> Aromatic phenylureas OR SN1 >> Nitrenium Ion formation >> Primary (unsaturated) heterocyclic amine OR SN1 >> Nitrenium Ion formation >> Primary aromatic amine OR SN1 >> Nitrenium Ion formation >> Secondary aromatic amine OR SN1 >> Nitrenium Ion formation >> Tertiary aromatic amine OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic azo OR SN1 >> Nitrenium Ion formation >> Unsaturated heterocyclic nitro OR SN2 OR SN2 >> Direct Acting Epoxides and related OR SN2 >> Direct Acting Epoxides and related >> Aziridines OR SN2 >> Direct Acting Epoxides and related >> Epoxides OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> Nitrosation-SN2 OR SN2 >> Nitrosation-SN2 >> Nitroso-SN2 OR SN2 >> P450 Mediated Epoxidation OR SN2 >> P450 Mediated Epoxidation >> Thiophenes-SN2 OR SN2 >> SN2 at an sp3 Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by DNA binding by OECD

Domain logical expression index: "g"

Referential boundary: The target chemical should be classified as Aryl AND Diketone AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND Indandione AND Pyridine AND Quinoline/ Isoquinoline by Organic Functional groups

Domain logical expression index: "h"

Referential boundary: The target chemical should be classified as Fused carbocyclic aromatic AND Indandione AND Overlapping groups AND Quinoline/ Isoquinoline by Organic Functional groups (nested)

Domain logical expression index: "i"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Carbonyl, aliphatic attach [-C(=O)-] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "j"

Referential boundary: The target chemical should be classified as Aromatic compound AND Carbonyl compound AND Ketone by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "k"

Referential boundary: The target chemical should be classified as Non binder, without OH or NH2 group by Estrogen Receptor Binding

Domain logical expression index: "l"

Referential boundary: The target chemical should be classified as Moderate binder, NH2 group OR Moderate binder, OH grooup OR Non binder, impaired OH or NH2 group OR Non binder, MW>500 OR Non binder, non cyclic structure OR Strong binder, NH2 group OR Strong binder, OH group OR Weak binder, NH2 group OR Weak binder, OH group OR Very strong binder, OH group by Estrogen Receptor Binding

Domain logical expression index: "m"

Referential boundary: The target chemical should be classified as Aryl AND Diketone AND Fused carbocyclic aromatic AND Fused heterocyclic aromatic AND Indandione AND Pyridine AND Quinoline/ Isoquinoline by Organic Functional groups

Domain logical expression index: "n"

Referential boundary: The target chemical should be classified as Fused carbocyclic aromatic AND Indandione AND Overlapping groups AND Quinoline/ Isoquinoline by Organic Functional groups (nested)

Domain logical expression index: "o"

Referential boundary: The target chemical should be classified as Aliphatic Carbon [CH] AND Aromatic Carbon [C] AND Aromatic Nitrogen AND Carbonyl, aliphatic attach [-C(=O)-] AND Carbonyl, olefinic attach [-C(=O)-] AND Carbonyl, one aromatic attach [-C(=O)-] AND Miscellaneous sulfide (=S) or oxide (=O) AND Olefinic carbon [=CH- or =C<] AND Tertiary Carbon by Organic functional groups (US EPA)

Domain logical expression index: "p"

Referential boundary: The target chemical should be classified as Aromatic compound AND Carbonyl compound AND Ketone by Organic functional groups, Norbert Haider (checkmol)

Domain logical expression index: "q"

Referential boundary: The target chemical should be classified as No alert found by Protein binding by OECD

Domain logical expression index: "r"

Referential boundary: The target chemical should be classified as Acylation OR Acylation >> Direct Acylation Involving a Leaving group OR Acylation >> Direct Acylation Involving a Leaving group >> Acetates OR Acylation >> Direct Acylation Involving a Leaving group >> Acyl halides (including benzyl and carbamoyl deriv.) OR Acylation >> Direct Acylation Involving a Leaving group >> Anhydrides OR Acylation >> Direct Acylation Involving a Leaving group >> Azlactone OR Acylation >> Direct Acylation Involving a Leaving group >> Sulphonyl halides OR Acylation >> Isocyanates and Related Chemicals OR Acylation >> Isocyanates and Related Chemicals >> Isothiocyanates OR Acylation >> Ring Opening Acylation OR Acylation >> Ring Opening Acylation >> alpha-Lactams OR Michael addition OR Michael addition >> Polarised Alkenes OR Michael addition >> Polarised Alkenes >> Polarised alkene - amides OR Michael addition >> Polarised Alkenes >> Polarised alkene - esters OR Michael addition >> Polarised Alkenes >> Polarised alkene - ketones OR Michael addition >> Quinones and Quinone-type Chemicals OR Michael addition >> Quinones and Quinone-type Chemicals >> Pyranones (and related nitrogen chemicals) OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-diimine OR Michael addition >> Quinones and Quinone-type Chemicals >> Quinone-imine OR Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> 1-3-Dicarbonyls OR Schiff Base Formers >> Direct Acting Schiff Base Formers >> Mono-carbonyls OR SN2 OR SN2 >> Episulfonium Ion Formation OR SN2 >> Episulfonium Ion Formation >> Mustards OR SN2 >> Epoxides and Related Chemicals OR SN2 >> Epoxides and Related Chemicals >> Epoxides OR SN2 >> SN2 reaction at a sulphur atom OR SN2 >> SN2 reaction at a sulphur atom >> Thiols OR SN2 >> SN2 reaction at sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl diazo OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl halides OR SN2 >> SN2 reaction at sp3 carbon atom >> Allyl acetates and related chemicals OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Haloalkenes (and related cyano, sulfate and sulfonate subs. chem.) OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls (and related cyano, sulfate and sulphonate subs. chem.) OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halocarbonyls OR SN2 >> SN2 reaction at sp3 carbon atom >> beta-Halo ethers OR SN2 >> SN2 reaction at sp3 carbon atom >> Sulfonates OR SNAr OR SNAr >> Nucleophilic aromatic substitution OR SNAr >> Nucleophilic aromatic substitution >> Activated halo-benzenes OR SNAr >> Nucleophilic aromatic substitution >> Halo-triazines by Protein binding by OECD

Domain logical expression index: "s"

Referential boundary: The target chemical should be classified as Not known precedent reproductive and developmental toxic potential by DART scheme v.1.0

Domain logical expression index: "t"

Referential boundary: The target chemical should be classified as Known precedent reproductive and developmental toxic potential OR Triazole derivatives (13c) OR Tubolin interactors.Benzimidazole-like derivatives for metabolites (6b-1) OR Tubolin interactors.Benzimidazole-like derivatives for metabolites (6b-1) >> Benzimidazole-like derivatives / Metabolite  by DART scheme v.1.0

Domain logical expression index: "u"

Parametric boundary:The target chemical should have a value of log Kow which is >= 1.48

Domain logical expression index: "v"

Parametric boundary:The target chemical should have a value of log Kow which is <= 4.31

Conclusions:
The developmental toxicity LOEL (Lowest Observed Effect Level) of D&C Yellow No. 11 in Sprague Dawley rat by the oral route was estimated to be 99.1999 mg/kg bw/day.
Executive summary:

The developmental toxicity LOEL (Lowest Observed Effect Level) of D&C Yellow No. 11 in Sprague Dawley rat by the oral route was estimated to be 99.1999 mg/kg bw/day.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
adverse effect observed
99.2 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
K2 data from the Qsar Prediction.
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

The developmental toxicity LOEL (Lowest Observed Effect Level) of D&C Yellow No. 11 in Sprague Dawley rat by the oral route was estimated to be 99.1999 mg/kg bw/day.

Justification for selection of Effect on developmental toxicity: via oral route:

The developmental toxicity LOEL (Lowest Observed Effect Level) of D&C Yellow No. 11 in Sprague Dawley rat by the oral route was estimated to be 99.1999 mg/kg bw/day.

Justification for classification or non-classification

D&C Yellow No. 11 is found to exhibit non toxic reproductive effects at higher doses in a 125 weeks toxicity study in rats. However, the majority use of this chemical is used as a solvent form to color topical drug preparations and cosmetics. Thus, exposure to high levels of direct D&C Yellow No. 11 is likely to be minimal and hence the chemical has not be considered as toxic to reproduction and developmental toxicity for classification.