Octyl acetate

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from peer-reviewed journal

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)

Principles of method if other than guideline:

Teratogenic Potential toxicity study of Octyl Acetate in Rats

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories
- Age at study initiation: (P) x wks; 9 weeks old
- Weight at study initiation: 212 - 216 g female
- Fasting period before study: No data available
- Housing: Animals were housed individually (except during the first week of quarantine and during mating) in suspended stainless-steel cages and All animals were identified by uniquely numbered ear tags during the course of the study.
- Diet (e.g. ad libitum): Food (certified Rodent Chow, Ralston Punna Co.)
- Water (e.g. ad libitum): water, ad libitum
- Acclimation period: 3-week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19- 24 °C (monitored daily)
- Humidity (%): 40-70% (monitored daily)
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): 12-hr photoperiod

IN-LIFE DATES: From: To: No data available

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

water

Remarks:

Distilled

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: Octyl acetate was dissolved in distilled water to give as dose of 0, 100, 500 or 1000 mg/Kg

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Distilled water
- Concentration in vehicle: 0, 100, 500 or 1000 mg/Kg
- Amount of vehicle (if gavage): Dose volumes were based on GD 6 body weights throughout the dosing period
- Lot/batch no. (if required): No data
- Purity: No data

Details on mating procedure:

- M/F ratio per cage: No data avaialble
- Length of cohabitation: No data avaialble
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy Copulatory plug in the vagina
or by observation of sperm in a vaginal rinse were referred to as day 0 of pregnancy
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. No data avaialble
- Further matings after two unsuccessful attempts: [no / yes (explain)] No data avaialble
- After successful mating each pregnant female was caged (how): Individually
- Any other deviations from standard protocol: No data avaialble

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

10 days

Frequency of treatment:

Daily

Details on study schedule:

- Rationale for animal assignment (if not random): Females confirmed to have mated were randomly assigned to one of four experimental groups of 22 mated female rats.

Remarks:

Doses / Concentrations:
0, 100, 500 and 1000 mg/Kg
Basis:

No. of animals per sex per dose:

Total: 85
0 mg/kg bw : 22 female
100 mg/kg bw :20 female
500 mg/kg bw :22 female
1000 mg/kg bw :21 female

Control animals:

yes, concurrent vehicle

Details on study design:

No data avaialble

Positive control:

No data avaialble

Parental animals: Observations and examinations:

Survival, clinical sign, body weight and body weight change and food consumption were observed.

Oestrous cyclicity (parental animals):

Corpora lutea and Resorptions were examined.

Sperm parameters (parental animals):

No data available

Litter observations:

Fetuses weighe and sexed were examined.

Postmortem examinations (parental animals):

Organ weight and gross pathology were examined.

Postmortem examinations (offspring):

Examined externally for gross abnormalities, visceral, and skeletal malformations and variations, and crown-rump distance were measured.

Statistics:

Maternal body weight and body weight change, food consumption, uterine data (i.e., corpora lutea, implants, resorptions), and malformation data were analyzed statistically using
Bartlett's test of homogeneity of variance (Snedecor and Cochran, 1967) was used to determine if the groups had equivalent variances at the 1 % level of significance. If the variances were not significantly different, the groups were compared using a standard one-way analysis of variance (ANOVA). If significant differences among the means were indicated, Duncan's test (Dunnett, 1964) was performed to determine which treated groups differed from control. Fetal weights and crown-rump lengths were analyzed using individual fetal values by a standard nested analysis of variance, with values nested within dams and dams nested within groups. If differences in groups were indicated, the least-significantdifference technique (Snedecor and Cochran, 1967) was used to determine which treated groups differed from control.
If the groups did not have equivalent variances at the 1 % level, then a Kruskal-Wallis test (nonparametric) was used to assess differences in group means (Hollander and Wolf, 1973). If the means were different, a rank sum comparison was used to determine which treatment groups differed from control.

Reproductive indices:

No data avaialble

Offspring viability indices:

No data avaialble

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:

no effects observed

Histopathological findings: non-neoplastic:

not specified

Other effects:

not specified

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

not specified

Reproductive performance:

no effects observed

Moraltity:
When treated with 1000 mg/kg bw, 2 female rats were died one each on GDs 10 and
12, respectively.
No effect on mortality of 100 and 500 mg/kg bw treated female rats were observed as compared to control.

Clinical signs:
When treated with 1000 mg/kg bw, elevated incidences of alopecia, rales, red nasal discharge, and anal-genital staining were observed in treated female rats ascompared to control.

Body weight:
When treated with 1000 mg/kg bw, A statistically significant decreased in mean body weight on on GDs 9, 12, 16, and 20 were observed as compared with control. The effect was most evident during the first several days of dosing, when these animals actually lost weight (GDs 6-9).

When treated with 500 mg/kg bw, Statistically significant decrase in mean body weight and body weight changes were observed at several time points as compared with control. These decrase in body weight appeared to occur in an ordered response to dose.

Food consumption:
When treated with 500 and 1000 mg/kg bw, dose-related decreases in food consumption for the Day 6-9, 9-12, and 12- 16 intervals were observed as
compared with control.

Reproductive function: estrous cycle
When treated with 1000 mg/kg bw, slight increase in resorptions were observed as compared to control. But, the difference was not statistically significant.

Reproductive performance: No statistically significant effect were observed on Corpora lutea/dam, Implants/litter, Resorptions/litter and Live fetuses/litter as compared to control.

Organ weights: No statistically significant effect were observed Uterine weight of treated female rats as compared to control.

Dose descriptor:

NOAEL

Effect level:

500 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

other: No effect on survival, clinical sign, body weight, food consumption, reproductive performance and organ weight

Clinical signs:

not specified

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

Moraltity:
No significant effect was observed on Live fetuses/litter s compared to control.

Body weight:
No significant effect was observed on fetal body weight as compared to control.

Gross pathology:
Tail absent were observed in 1000 mg/kg bw and micrognathia in 500 mg/kg bw as compared to control.

No significant differences or dose-related change were observed on crown rump distance of fetuses were observed as compared to control.

Histopathology:
Visceral examinations:
When treated wtih 1000 mg/kg bw, dilated lateral cerebral ventricles in two fetuses were observed which are anatomical variations previously observed in historical control fetuses.

Skeletal malformations:
When treated wtih 1000 mg/kg bw, Different types of vertebral malformations were observed in four fetuses (four litters) in the form of incomplete ossification but, was not statistically significant as compated to control.

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No effect on body weight, gross pathology and histopathology

Reproductive effects observed:

not specified

Maternal Body Weight And Body Weight Changes^a

	Dose group
Gestational day	0 g/kg (N=20)	0.1 g/kg (N=20)	0.5 g/kg (N=20)	1. 0 g/kg (N=20)
	Body weight (g)
0	216.7 ±22.5	214.8 ± 16.0	213.7 ± 18.3	212.0± 18.5
3	233.3 ±22.4	232.0 ±17.2	230.1 ± 17.8	227.9 ±19.2
6	248.8 ± 23.0	246.1 ±17.8	244.6 ± 20.0	242.9 ± 20.2
9	261.0 ±24.9	256.6 ±18.4	247.3 ±21.2	234.7 ±24.5**
12	279.9 ± 24.3	273.7 ±19.9	261.1 ±23.4*	247.0 ±25.4"
16	306.5 ± 26.0	300.0 ±23.5	288.0 ±27.1	275.3 ± 24.7**
20	368.5 ±28.0	361.3 ±27.7	352.4 ±34.9	338.1 ±26.7*
20^c	295.3 ±23.0	285.6 ±21.1	272.1 ±26.0*	265.1 ±24.3**
	Body weight change (g)
0-6	32.0 ± 3.8	31.3 ± 4.8	30.9 ± 6.8	30.9 ± 6.0
6-9	12.2 ± 4.1	10.6 ± 5.1	2.7 ± 11.3**	-8.1 ± 12.1**
9-12	18.9 ± 4.2	17.1 ± 4.1	13.8 ± 9.4*	13.5 ± 7.9*
12-16	26.6 ± 6.9	26.3 ± 5.6	26.9 ± 8.6	27.3 ± 8.5
16-20	62.0 ± 6.6	61.3 ± 9.0	64.4 ± 10.8	62.8 ± 5.5
0-20	151.8 ± 13.9	146.5 ± 16.4	138.6 ±25.9	126.3 ± 15.5**
6-20^c	46.6 ± 8.5	39.6 ± 9.6	28.8 ±15.0**	22.2 ± 13.3**

^aValues are means ± SD. N = number of dams.

^b From Day 12, W =20; from Day 16, N= 19.

c Body weight corrected for gravid uterine weight.

* Significantly different from control, p≤0.05.

** Significantly different from control, p≤0.01.

Mean food consumption of pregnant rats^a

	Dose group
Gestational day	0 g/kg	0.1 g/kg	0.5 g/kg	1.0 g/kg
0-3	69.2+ 5.9	69.8 ± 5.6	69.2+ 5.7	67.6 ± 5.7
	(21)*	(19)	(22)	(21)
3-6	76.4+ 6.8	72.3 ± 7.8	73.3 ± 6.2	72.5 ± 5.7
	(20)	(18)	(22)	(21)
6-9	76.7 ± 8.1	72.8 ± 7.2	63.7 ± 11.1"	49.3 ±12.3**
	(22)	(19)	(22)	(21)
9-12	80.7 ± 7.5	75.5 ± 8.5	66.9 ± 9.4"	60.5 ± 19.2"
	(21)	(H)	(21)	(18)
12-16	104.3 ± 10.5	101.8 ± 11.9	92.4+ 13.2*	88.8 ± 9.4"
	(22)	(19)	(19)	(19)
16-20	112.7 db 8.5	111.9± 11.6	109.8 ± 14.0	110.0 ± 10.9
	(22)	(20)	(22)	(19)

^aValues are the means ± SD of the amount of diet consumed expressed in grams per rat.

* N is given in parentheses.

* Significantly different from control, p≤ 0.05.

** Significantly different from control, p≤0.01.

Uterine Implantation Data^a

	Dose group
	0 g/kg (N=20)	0.1 g/Kg (N = 20)	0.5 g/kg (N=20)	1.0 g/kg (N =20)
Corpora lutea/dam	16.0 ± 1.6	15.9 ± 2.2	16.1 ± 2.5	16.5 ±2.6
Implants/litter	14.7 ± 1.5	14.7 ± 2.0	14.9 ± 2.1	14.8 ± 1.9
Resorptions/litter	0.6 ±0.7	0.9 ± 1.2	0.6 ± 0.8	1.3± 1.4
Uterine weight (g)	74.9 ± 9.0	75.6 ±12.1	77.8± 13.1	73.0 ±8.8
Live fetuses/litter	7.9 ± 1.9	7.4 ± 1.8	7.0 ± 1.8	6.7 ±2.2
Male	6.2 ±1.6	6.3 ± 1.8	7.2 ± 1.6	6.8 ± 1.9
Female	14.1 ± 1.6	13.7 ± 2.2	14.2 ± 2.0	13.5 ± 1.7
Total	16.0 ± 1.6	15.9 ± 2.2	16.1 ± 2.5	16.5 ±2.6

^aValues are means ± SD. N = number of litters.

Conclusions:

NOAEL was considered to be 500 mg/kg bw for P generation and 1000 mg/kg bw for F1 generation when Sprague-Dawley female rats were treated with Octyl Acetate orally by gavage for 10 days of gestation.

Executive summary:

In a Teratogenicity study, Sprague-Dawley female rats were treated withOctyl Acetate in the concentration of 0,100, 500 and 1000 mg/kg bw orally by gavage.2 female rats were died at 1000 mg/kg bw one each on GDs 10 and 12, respectively and elevated incidences of alopecia, rales, red nasal discharge, and anal-genital staining were observed in treated female rats as compared to control. A statistically significant decreased in mean body weight on on GDs 9, 12, 16, and 20 were observed at 1000 mg/kg bw.The effect was most evident during the first several days of dosing, when these animals actually lost weight (GDs 6-9).Statistically significant decrase in mean body weight and body weight changes were observed at several time points at 500 mg/kg bw as compared with control. These decrease in body weight appeared to occur in an ordered response to dose. Similarly, Dose-related decreases in food consumption for the Day 6-9, 9-12, and 12- 16 intervals were observed at 500 and 1000 mg/kg bw as compared with control. Slight increase in resorptions was observed as compared to control. But, the difference was not statistically significant. In addition, No statistically significant effect were observed on Corpora lutea/dam, Implants/litter, Resorptions/litter and Live fetuses/litter and Uterine weight of treated female rats as compared to control in P generation. In F1 generation,No significant effect was observed on fetal body weight as compared to control.Tail absent were observed in 1000 mg/kg bw and micrognathia in 500 mg/kg bwas compared to control. No significant differences or dose-related change were observed on crown rump distance of fetuses were observed as compared to control.Dilated lateral cerebral ventricles in two fetuses were observed at 1000 mg/kg bw which are anatomical variations previously observed in historical control fetuses. Different types of vertebral malformations were observed in four fetuses (four litters) in the form of incomplete ossification at 1000 mg/kg bw. But, were not statistically significant as compared to control. Therefore,NOAEL was considered to be 500 mg/kg bw for P generation and 1000 mg/kg bw for F1 generation whenSprague-Dawley female rats were treated withOctyl Acetate orally by gavage for 10 days of gestation.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

500 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is from peer reviewed journal

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Reproductive toxicity:

Based on the data available for target Acetate C-8 (CAS no 112-14-1) is summarized below

In a study conducted by Daughtreyet al(1989), Teratogenicity was evaluated in Sprague-Dawley female rats by using Octyl Acetate in the concentration of 0, 100, 500 and 1000 mg/kg bw orally by gavage. 2 female rats were died at 1000 mg/kg bw one each on GDs 10 and 12, respectively and elevated incidences of alopecia, rales, red nasal discharge, and anal-genital staining were observed in treated female rats as compared to control. A statistically significant decreased in mean body weight on on GDs 9, 12, 16, and 20 were observed at 1000 mg/kg bw. The effect was most evident during the first several days of dosing, when these animals actually lost weight (GDs 6-9). Statistically significant decrase in mean body weight and body weight changes were observed at several time points at 500 mg/kg bw as compared with control. These decrease in body weight appeared to occur in an ordered response to dose. Similarly, Dose-related decreases in food consumption for the Day 6-9, 9-12, and 12- 16 intervals were observed at 500 and 1000 mg/kg bw as compared with control. Slight increase in resorptions was observed as compared to control. But, the difference was not statistically significant. In addition, No statistically significant effect were observed on Corpora lutea/dam, Implants/litter, Resorptions/litter and Live fetuses/litter and Uterine weight of treated female rats as compared to control in P generation. In F1 generation, No significant effect was observed on fetal body weight as compared to control. Tail absent were observed in 1000 mg/kg bw and micrognathia in 500 mg/kg bw as compared to control. No significant differences or dose-related change were observed on crown rump distance of fetuses were observed as compared to control. Dilated lateral cerebral ventricles in two fetuses were observed at 1000 mg/kg bw which are anatomical variations previously observed in historical control fetuses. Different types of vertebral malformations were observed in four fetuses (four litters) in the form of incomplete ossification at 1000 mg/kg bw. But, were not statistically significant as compared to control. Therefore, NOAEL was considered to be 500 mg/kg bw for P generation and 1000 mg/kg bw for F1 generation when Sprague-Dawley female rats were treated with Octyl Acetate orally by gavage for 10 days of gestation.

In a repeated dose oral toxicity study, Sprague-Dawley male rats were treated with Octyl Acetate in the concentration of 0, 100, 500 and 1000 mg/kg bw orally by gavage. One male rat died on Day 15 of the study. This death was due to accidental instillation of test material into the lungs during the oral gavage procedure. There were no other deaths during the study and all animals survived until the scheduled termination. Decrase in body weight and food consumption were observed in treated male and female rats as compared to control but not statistically significant. No significant treatment-related ocular effects were observed in treated male and female rats as compared to control. The few lesions which were observed were considered to be common in rats of this age. Similarly, No statistically significant effects were observed on hematology and clinical chemistry of treated male and female rats as compared to control. Statistically significant deviations were observed in albumin, potassium, and alanine aminotransferase level of treated male and female rats as compared to control. However, since the observed differences were small and not evident in other treatment groups, they were not judged to be biologically important. In addition, increased in absolute liver weights and relative kidney weight were observed at 1000 mg/kg bw treated male and female rats as compared to control. Increase in absolute liver weights was not statistically significant. Increased in relative liver weights were observed at 100 and 500 mg/kg bw treated male and female rats as compared to control. No significant effect on absolute and relative Testes weights were observed in treated male rats as compared to control. Mottled lung discoloration was observed at 500 and 1000 mg/kg bw treated male and female rats as compared to control. This observation most likely stemmed from occasional instances in which the test material was aspirated. Mild tubular nephropathy was observed at 1000 mg/kg bw treated male rats as compared to control. However, these findings were not observed in high-dose females or in either sex of the 100 and 500 mg/kg bw animals. Therefore, NOAEL was considered to be 1000 mg/kg bw when Sprague-Dawley male rats were treated with Octyl Acetate orally by gavage for 13 weeks.

Thus, based on the available data for target Acetate C-8 (CAS no 112-14-1) is likely to be non hazardous as reproductive toxicant.

Short description of key information:

Acetate C-8 (CAS no 112-14-1) is likely to be non hazardous as reproductive toxicant.

Justification for selection of Effect on fertility via oral route:

NOAEL was considered to be 500 mg/kg bw for P generation and 1000 mg/kg bw for F1 generation when Sprague-Dawley female rats were treated with Octyl Acetate orally by gavage for 10 days of gestation.

Effects on developmental toxicity

Description of key information

Acetate C-8  is likely to be non hazardous as developmental toxicant.

Link to relevant study records

Reference

Endpoint:

developmental toxicity

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from peer-reviewed journal

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Principles of method if other than guideline:

Teratogenic Potential toxicity study of Octyl Acetate in Rats

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Sex: Female
- Source: Charles River Breeding Laboratories
- Age at study initiation: (P) x wks; 9 weeks old
- Weight at study initiation: 212 - 216 g female
- Fasting period before study: No data available
- Housing: Animals were housed individually (except during the first week of quarantine and during mating) in suspended stainless-steel cages and All animals were identified by uniquely numbered ear tags during the course of the study.
- Diet (e.g. ad libitum): Food (certified Rodent Chow, Ralston Punna Co.)
- Water (e.g. ad libitum): water, ad libitum
- Acclimation period: 3-week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19- 24 °C (monitored daily)
- Humidity (%): 40-70% (monitored daily)
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): 12-hr photoperiod

IN-LIFE DATES: From: To: No data available

Route of administration:

oral: gavage

Type of inhalation exposure (if applicable):

not specified

Vehicle:

water

Remarks:

Distilled

Details on exposure:

PREPARATION OF DOSING SOLUTIONS: Octyl acetate was dissolved in distilled water to give as dose of 0, 100, 500 or 1000 mg/Kg

DIET PREPARATION
- Rate of preparation of diet (frequency): No data
- Mixing appropriate amounts with (Type of food): No data
- Storage temperature of food: No data

VEHICLE
- Justification for use and choice of vehicle (if other than water): Distilled water
- Concentration in vehicle: 0, 100, 500 or 1000 mg/Kg
- Amount of vehicle (if gavage): Dose volumes were based on GD 6 body weights throughout the dosing period
- Lot/batch no. (if required): No data
- Purity: No data

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

- M/F ratio per cage: No data avaialble
- Length of cohabitation: No data avaialble
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy Copulatory plug in the vagina
or by observation of sperm in a vaginal rinse were referred to as day 0 of pregnancy
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. No data avaialble
- Further matings after two unsuccessful attempts: [no / yes (explain)] No data avaialble
- After successful mating each pregnant female was caged (how): Individually
- Any other deviations from standard protocol: No data avaialble

Duration of treatment / exposure:

10 days

Frequency of treatment:

Daily

Duration of test:

Gestation days-20

Remarks:

Doses / Concentrations:
0, 100, 500 and 1000 mg/kg bw
Basis:

No. of animals per sex per dose:

Total: 85
0 mg/kg bw : 22 female
100 mg/kg bw :20 female
500 mg/kg bw :22 female
1000 mg/kg bw :21 female

Control animals:

yes, concurrent vehicle

Details on study design:

No data avaialble

Maternal examinations:

Survival, clinical sign, body weight and body weight change, food consumption, Organ weight and gross pathology were examined.

Ovaries and uterine content:

Corpora lutea and Resorptions were examined

Fetal examinations:

Fetuses weighe and sexed, Examined externally for gross abnormalities, visceral, and skeletal malformations and variations, and crown-rump distance were measured.

Statistics:

Maternal body weight and body weight change, food consumption, uterine data (i.e., corpora lutea, implants, resorptions), and malformation data were analyzed statistically using Bartlett's test of homogeneity of variance (Snedecor and Cochran, 1967) was used to determine if the groups had equivalent variances at the 1 % level of significance. If the variances were not significantly different, the groups were compared using a standard one-way analysis of variance (ANOVA). If significant differences among the means were indicated, Duncan's test (Dunnett, 1964) was performed to determine which treated groups differed from control. Fetal weights and crown-rump lengths were analyzed using individual fetal values by a standard nested analysis of variance, with values nested within dams and dams nested within groups. If differences in groups were indicated, the least-significantdifference technique (Snedecor and Cochran, 1967) was used to determine which treated groups differed from control. If the groups did not have equivalent variances at the 1 % level, then a Kruskal-Wallis test (nonparametric) was used to assess differences in group means (Hollander and Wolf, 1973). If the means were different, a rank sum comparison was used to determine which treatment groups differed from control.

Indices:

No data avaialble

Historical control data:

No data avaialble

Clinical signs:

not specified

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

not specified

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Number of abortions:

not specified

Pre- and post-implantation loss:

not specified

Total litter losses by resorption:

not specified

Early or late resorptions:

not specified

Dead fetuses:

not specified

Changes in pregnancy duration:

not specified

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified

Changes in number of pregnant:

not specified

Other effects:

not specified

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Moraltity:
When treated with 1000 mg/kg bw, 2 female rats were died one each on GDs 10 and 12, respectively.

No effect on mortality of 100 and 500 mg/kg bw treated female rats were observed as compared to control.

Clinical signs:
When treated with 1000 mg/kg bw, elevated incidences of alopecia, rales, red nasal discharge, and anal-genital staining were observed in treated female rats as compared to control.

Body weight:
When treated with 1000 mg/kg bw, A statistically significant decreased
in mean body weight on on GDs 9, 12, 16, and 20 were observed as compared with control.
The effect was most evident during the first several days of dosing, when these animals actually lost weight (GDs 6-9).

When treated with 500 mg/kg bw, Statistically significant decrase in mean body weight and body weight changes were observed at several time points as compared with control.
These decrase in body weight appeared to occur in an ordered response to dose.

Food consumption:
When treated with 500 and 1000 mg/kg bw, dose-related decreases in food consumption for the Day 6-9, 9-12, and 12- 16 intervals were observed as
compared with control.

Reproductive function: estrous cycle: When treated with 1000 mg/kg bw, slight increas in resorptions were observed as compared to control. But, the difference was not statistically significant.

Reproductive performance: No statistically significant effect were observed on Corpora lutea/dam, Implants/litter, Resorptions/litter and Live fetuses/litter as compared to control.

Organ weights: No statistically significant effect were observed Uterine weight of treated female rats as compared to control.

Dose descriptor:

NOAEL

Effect level:

500 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Abnormalities:

not specified

Localisation:

not specified

Description (incidence and severity):

not specified

Fetal body weight changes:

not specified

Description (incidence and severity):

Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified

Reduction in number of live offspring:

not specified

Changes in sex ratio:

not specified

Changes in litter size and weights:

not specified

Changes in postnatal survival:

not specified

External malformations:

not specified

Skeletal malformations:

not specified

Visceral malformations:

not specified

Other effects:

not specified

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Moraltity:
No significant effect was observed on Live fetuses/litter s compared to control.

Body weight:
No significant effect was observed on fetal body weight as compared to control.

Gross pathology:
Tail absent were observed in 1000 mg/kg bw and micrognathia in 500 mg/kg bw as compared to control.

No significant differences or dose-related change were observed on crown rump distance of fetuses were observed as compared to control.

Histopathology:
Visceral examinations:
When treated wtih 1000 mg/kg bw, dilated lateral cerebral ventricles in two fetuses were observed which are anatomical variations previously observed in historical control fetuses.

Skeletal malformations:
When treated wtih 1000 mg/kg bw, Different types of vertebral malformations were observed in four fetuses (four litters) in the form of incomplete ossification but, was not statistically significant as compated to control.

Remarks on result:

not measured/tested

Abnormalities:

not specified

Developmental effects observed:

not specified

Uterine Implantation Data^a

	Dose group
	0 g/kg (N=20)	0.1 g/Kg (N = 20)	0.5 g/kg (N=20)	1.0 g/kg (N =20)
Corpora lutea/dam	16.0 ± 1.6	15.9 ± 2.2	16.1 ± 2.5	16.5 ±2.6
Implants/litter	14.7 ± 1.5	14.7 ± 2.0	14.9 ± 2.1	14.8 ± 1.9
Resorptions/litter	0.6 ±0.7	0.9 ± 1.2	0.6 ± 0.8	1.3± 1.4
Uterine weight (g)	74.9 ± 9.0	75.6 ±12.1	77.8± 13.1	73.0 ±8.8
Live fetuses/litter	7.9 ± 1.9	7.4 ± 1.8	7.0 ± 1.8	6.7 ±2.2
Male	6.2 ±1.6	6.3 ± 1.8	7.2 ± 1.6	6.8 ± 1.9
Female	14.1 ± 1.6	13.7 ± 2.2	14.2 ± 2.0	13.5 ± 1.7
Total	16.0 ± 1.6	15.9 ± 2.2	16.1 ± 2.5	16.5 ±2.6

^aValues are means ± SD. N = number of litters.

Conclusions:

NOAEL was considered to be 500 mg/kg bw for P generation and 1000 mg/kg bw for F1 generation when Sprague-Dawley female rats were treated with Octyl Acetate orally by gavage for 10 days of gestation.

Executive summary:

In aTeratogenicity study, Sprague-Dawley female rats were treated withOctyl Acetate in the concentration of0,100, 500 and 1000 mg/kg bworally by gavage.2 female rats were died at 1000 mg/kg bw one each on GDs 10 and 12, respectively and elevated incidences of alopecia, rales, red nasal discharge, and anal-genital staining were observed in treated female rats as compared to control. A statistically significant decreased in mean body weight on on GDs 9, 12, 16, and 20 were observed at 1000 mg/kg bw.The effect was most evident during the first several days of dosing, when these animals actually lost weight (GDs 6-9).Statistically significant decrase in mean body weight and body weight changes were observed at several time points at 500 mg/kg bw as compared with control. These decrease in body weight appeared to occur in an ordered response to dose. Similarly, Dose-related decreases in food consumption for the Day 6-9, 9-12, and 12- 16 intervals were observed at 500 and 1000 mg/kg bw as compared with control. Slight increase in resorptions was observed as compared to control. But, the difference was not statistically significant. In addition, No statistically significant effect were observed on Corpora lutea/dam, Implants/litter, Resorptions/litter and Live fetuses/litter and Uterine weight of treated female rats as compared to control in P generation. In F1 generation,No significant effect was observed on fetal body weight as compared to control.Tail absent were observed in 1000 mg/kg bw and micrognathia in 500 mg/kg bwas compared to control. No significant differences or dose-related change were observed on crown rump distance of fetuses were observed as compared to control.Dilated lateral cerebral ventricles in two fetuses were observed at 1000 mg/kg bw which are anatomical variations previously observed in historical control fetuses. Different types of vertebral malformations were observed in four fetuses (four litters) in the form of incomplete ossification at 1000 mg/kg bw. But, were not statistically significant as compared to control. Therefore,NOAEL was considered to be 500 mg/kg bw for P generation and 1000 mg/kg bw for F1 generation whenSprague-Dawley female rats were treated withOctyl Acetate orally by gavage for 10 days of gestation.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

Data is from peer reviewed journal

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

Development toxicity:

Based on the data available for target Acetate C-8 (CAS no 112-14-1) is summarized below

In a study conducted by Daughtreyet al(1989), Teratogenicity was evaluated in Sprague-Dawley female rats by using Octyl Acetate in the concentration of 0, 100, 500 and 1000 mg/kg bw orally by gavage. 2 female rats were died at 1000 mg/kg bw one each on GDs 10 and 12, respectively and elevated incidences of alopecia, rales, red nasal discharge, and anal-genital staining were observed in treated female rats as compared to control. A statistically significant decreased in mean body weight on on GDs 9, 12, 16, and 20 were observed at 1000 mg/kg bw. The effect was most evident during the first several days of dosing, when these animals actually lost weight (GDs 6-9). Statistically significant decrase in mean body weight and body weight changes were observed at several time points at 500 mg/kg bw as compared with control. These decrease in body weight appeared to occur in an ordered response to dose. Similarly, Dose-related decreases in food consumption for the Day 6-9, 9-12, and 12- 16 intervals were observed at 500 and 1000 mg/kg bw as compared with control. Slight increase in resorptions was observed as compared to control. But, the difference was not statistically significant. In addition, No statistically significant effect were observed on Corpora lutea/dam, Implants/litter, Resorptions/litter and Live fetuses/litter and Uterine weight of treated female rats as compared to control in P generation. In F1 generation, No significant effect was observed on fetal body weight as compared to control. Tail absent were observed in 1000 mg/kg bw and micrognathia in 500 mg/kg bw as compared to control. No significant differences or dose-related change were observed on crown rump distance of fetuses were observed as compared to control. Dilated lateral cerebral ventricles in two fetuses were observed at 1000 mg/kg bw which are anatomical variations previously observed in historical control fetuses. Different types of vertebral malformations were observed in four fetuses (four litters) in the form of incomplete ossification at 1000 mg/kg bw. But, were not statistically significant difference as compared to control. Therefore, NOAEL was considered to be 500 mg/kg bw for P generation and 1000 mg/kg bw for F1 generation when Sprague-Dawley female rats were treated with Octyl Acetate orally by gavage for 10 days of gestation.

Thus, based on the available data for target Acetate C-8 (CAS no 112-14-1) is likely to be non hazardous as developmental toxicant.

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

NOAEL was considered to be 500 mg/kg bw for P generation and 1000 mg/kg bw for F1 generation when Sprague-Dawley female rats were treated with Octyl Acetate orally by gavage for 10 days of gestation.

Justification for classification or non-classification

Based on the available data for target Acetate C-8 (CAS no 112-14-1) is likely to be non hazardous as reproductive and developmental toxicant.