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Description of key information

Acute toxicity:
Oral - LD50 = > 5 mL/kg
Inhalatiin - LC50 = > 511 ppm
Dermal: LD50 = > 10 mL/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Data considered reliable as copy of report received from the US EPA. Studies performed in accordance with 40 CFR part 716 for a chemical substance listed in Section 716.120 and processed for commercial purposes.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
According to Hagan, EC (1959) Acute Toxicity; Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, pp 17-25. Comparison with
OECD Test 401 suggests that with the exception of the absence of a control group and analysis of the formulations procedures and study design were similar to those prescribed in this guideline
GLP compliance:
not specified
Remarks:
GLP was just being introduced in 1978
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Summit View Farm Belvidere New Jersey USA
- Age at study initiation: Not reported
- Weight at study initiation: 139-164 g
- Fasting period before study: overnight prior to dosing
- Housing: assumed to be 5 animals/sex/group
- Diet (e.g. ad libitum): Wayne Animal Feeds available ad libitum except for overnight fast prior to dosing
- Water (e.g. ad libitum): ad libitum with possible exception of overnight prior to administration of test item
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not reported
- Humidity (%): Not reported
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): Not reported

IN-LIFE DATES: From: 16th March 1978To: 31st March 1978
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Test Item used as supplied
Doses:
0.5, 1.0, 2.0 and 5.0 mL/kg
No. of animals per sex per dose:
5 male and 5 female
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed for signs of pharmacologic activity and/or toxicitys 1, 3, 6 and 24 hours post dose and daily thereafter for a total of 14 days. Weighed on intitiation and termination of the study
- Necropsy of survivors performed: Yes
Statistics:
The LD50 was calculated, including the 95% confidence limits) where possible using the method of Litchfield and Wilcoxon (Litchfield JT and Wilcoxon F (1949) J Pharmacol. Exptl.Therap. pp96-99,
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
> 5 mL/kg bw
Based on:
test mat.
Remarks on result:
other: LD50 and 95% limits not calculable
Mortality:
One male animal given 5 mL/kg was sacrificed due to moribund condition on Day 5. Only signs observed from 24 hours after reciving the test item until sacrifice were slight depression and 28 g weight loss. No gross abnormalities at necropsy reported.
Clinical signs:
No clinical signs were oberved with the exception of 1 male dosed at 5.0 mL/kg that appeared slightly depressed within 24 hours of dosing and continued to Day 5 when it was humanely killed from the study.
Body weight:
There were no effects on body weight which could definitely be attributed to treatment. Two males gained less weight than expected than their counterparts. One of these (dosed at 0.5 mL/kg) was found to have fibrous tissue encasing the heart and lungs at necropsy and may have had an existing condition or been mis-dosed. The other animal, dosed at 1.0 mL/kg, gained a similar amount but did not show any signs clinical signs or abnormalities at necropsy. The male dosed at 5.0 mL/kg sacrificed due to ill health on Day 5 lost 28 g in the 5 days between administration of the test item and sacrifice.
Gross pathology:
With the exception of one male (dosed at 0.5 mL/kg) that was found to have fibrous tissue encasing the heart and lungs at necropsy, no abnormalities were found at gross necropsy of animals surviving the 14 day observation period.
Other findings:
None reported

One male rat given 5 ml/kg was sacrificed on day 5 following mild depression and bodyweight loss. In the absence of similar effects in other animals given the same dose this death may not be due to the test item.

Dose Level              Sex              Dead/Dosed              %            

                                                       (ml/kg)              5M:5F              0/5:0/5                     0

                                                               0.5            5M:5F              0/5:0/5                     0

1.0             5M:5F              0/5:0/5                     0

2.0             5M:5F              0/5:0/5                     0

5.0             5M:5F              0/5:0/5                     10

Result       LD50: > 5.0 ml/kg

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 was found to be greater than 5.0 mL/kg.
Executive summary:

Acute toxicity following administration of a single oral dose has been investigated in the rat. The LD50 was found to be in excess of 5 mL/kg body weight. At a density of 1.1181 the administered dose of 5 mL/kg equates to 5591 mg/kg body weight.

                                                                 
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 591 mg/kg bw
Quality of whole database:
Acute toxicity has been investigated in rats, mice and rabbits. All findings indicate the substance to exhibit low tow toxicity by the oral route

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Hazardous Substances Data Bank (HSDB®) is a toxicology data file on the National Library of Medicine's (NLM) Toxicology Data Network (TOXNET®). It focuses on the toxicology of potentially hazardous chemicals. It is enhanced with information on human exposure, industrial hygiene, emergency handling procedures, environmental fate, regulatory requirements, nanomaterials, and related areas. All data are referenced and derived from a core set of books, government documents, technical reports and selected primary journal literature. HSDB is peer-reviewed by the Scientific Review Panel (SRP), a committee of experts in the major subject areas within the data bank's scope. HSDB is organized into individual chemical records, and contains over 5000 such records. This study was performed before the introduction of OECD guidelines and GLP. Limited details available on methodology.
Principles of method if other than guideline:
To determine the effects, in rats, of acute inhalation exposure
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
No data
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Whole body inhalation chamber
- Exposure chamber volume: No data
- Method of holding animals in test chamber: No data
- Source and rate of air: No data
- Method of conditioning air: No data
- System of generating particulates/aerosols: Air was bubbled through diethyl phthalate at 150 deg C
- Method of particle size determination: No data
- Treatment of exhaust air: No data
- Temperature, humidity, pressure in air chamber: No data
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
6 h
Concentrations:
511 ppm (4.64 mg/L)
No. of animals per sex per dose:
3
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: No data
Statistics:
Not applicable
Sex:
not specified
Dose descriptor:
LC50
Effect level:
>= 511 ppm
Exp. duration:
6 h
Sex:
not specified
Dose descriptor:
LC50
Effect level:
>= 4.64 mg/L air (nominal)
Exp. duration:
6 h
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions in which this study was conducted LD50 was >511 ppm when administered by the inhalation route for 6 hours.
Executive summary:

Under the conditions in which this study was conducted, no mortality occurred when rats were exposed to a saturated vapour of 511 ppm (4.64 mg/L) by the inhalation route for 6 hours.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating conc.
Value:
4 640 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 - 31 March 1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in 1978 before the introduction of GLP and OECD methodology.
Qualifier:
according to guideline
Guideline:
other: Hagan EC (1959) Acute toxicity in Appraisal of the Safety of chemicals in foods, drugs and cosmetics, pp 17-25
Principles of method if other than guideline:
Four groups of 3male and 3 female albino rats were given doses of 1.0, 2.0, 5.0 and 10.0 ml/kg, applied to the shaved mildly abraded skin under an occlusive patch for 24 h then observed for 14 days. The DEP was used as received. Animals were observed for signs of pharmacologic activity and toxicity 1, 3, 6 and 24 hours post application and daily thereafter for a total of 14 days. Animals sacrificed at the end of the 14 day observation period were subjected to a complete gross necropsy.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Summit View Farm, Belvidere, New Jersey, USA
- Age at study initiation: Not reported
- Weight at study initiation: Males: 140 - 170g; females: 154 - 178g
- Fasting period before study: no
- Housing: standard laboratory conditions
- Diet (e.g. ad libitum): Wayne animal feed
- Water (e.g. ad libitum): yes
- Acclimation period: yes, period not specified

ENVIRONMENTAL CONDITIONS
- Temperature (°C): standard laboratory conditions
- Humidity (%): standard laboratory conditions
- Air changes (per hr): standard laboratory conditions
- Photoperiod (hrs dark / hrs light): standard laboratory conditions

IN-LIFE DATES: From: 16 March To: 31 March 1978
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Not reported
- % coverage: 10
- Type of wrap if used: gauze patches covered by an impermeable plastic wrapping

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: immediately

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.0, 2.0, 5.0 or 10 ml/kg
- Concentration (if solution): 100% as supplied
- Constant volume or concentration used: no
- For solids, paste formed: yes/no

VEHICLE
- Amount(s) applied (volume or weight with unit): N/A
- Concentration (if solution): N/A
- Lot/batch no. (if required): N/A
- Purity: N/A
Duration of exposure:
24 hours
Doses:
1.0, 2.0, 5.0 or 10 mL/kg
No. of animals per sex per dose:
3 males and 3 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs - 1, 3, 6 and 24 hours following dosing and daily thereafter for a total of 14 days. Body weight recorded at initiation and termination.
- Necropsy of survivors performed: yes
Statistics:
Not required as there were no deaths and an LD 50 could not be calculated.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 mL/kg bw
Based on:
test mat.
Mortality:
None in any dose group.
Clinical signs:
Skin slightly reddened in all animals when dressings removed
Body weight:
No definite effects in male rats and no effects in female rats.
Gross pathology:
No abnormalitities detected
Other findings:
None reported

LD50 > 10 ml/kg

Dose Level              Sex              Dead/dosed              % Mortality

(ml/kg)                      M:F

1.0                            3:3                    0/3:0/3                     0:0

2.0                            3:3                     0/3:0/3                     0:0

5.0                            3:3                     0/3:0/3                     0:0

10.0                         3:3                      0/3:0/3                     0:0

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
LD50 > 10 ml/kg
Executive summary:

Acute toxicity following administration of a single dermal dose over a 24 hour period has been investigated in the rat. The LD50 was determined to be in excess of 10 mL/kg body weight. This equates to a dose level of 11181 mg/kg when corrected for density.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
11 181 mg/kg bw

Additional information

Acute toxicity following administration of a single oral dose has been investigated in the rat. The LD50 was found to be in excess of 5 mL/kg body weight (5591 mg/kg when corrected for density).

A poorly documented study by the inhalation route indicates no mortality to have occurred when rats were exposed to a saturated vapour of 511 ppm (4.64 mg/L) by the inhalation route for 6 hours.

Acute toxicity following administration of a single dermal dose over a 24 hour period has been investigated in the rat. The LD50 was determined to be in excess of 10 mL/kg body weight (11181 mg/kg when corrected for density).


Justification for selection of acute toxicity – oral endpoint
Best documented of the studies available

Justification for selection of acute toxicity – inhalation endpoint
Single study available

Justification for selection of acute toxicity – dermal endpoint
Single study available

Justification for classification or non-classification

Acute toxicity has been investigated by the oral and dermal and inhalation routes of exposure. The outcome of these studies does not indicate a justification for classification according to the criteria of Regulation (EC) No. 1272/2008.