Glycerol, propoxylated, esters with acrylic acid

Endpoint summary

Description of key information

Oral: LD50 > 2000 mg/kg bw (male and female rats)

Inhalation: No study available

Dermal: LD50 > 2000 mg/kg bw (rabbit, occlusive)

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:

From June 15, 1992 to February 26, 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- Lot/batch No.: OF-20406

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd., Manston, Kent, U.K.
- Age at study initiation: 5- 8 wk
- Weight at study initiation: Males: 139 - 156 g; Females: 121 - 144 g
- Fasting period before study: Yes
- Housing: Solid-floor polypropylene cages with sawdust bedding
- Diet: ad libitum, Rat and Mouse Expanded Diet No.1, Special Diet Services Ltd.
- Water: ad libitum
- Acclimation period: At least 5 d

ENVIRONMENTAL CONDITIONS
- Temperature: 19- 23 °C
- Humidity: 47- 67%
- Air changes: 15/h
- Photoperiod: 12 h dark / 12h light

IN-LIFE DATES: From: 1992-06-15 to: 1992-07-07

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Dose volume: 1.91 mL/kg bw
Specific gravity: 1.050

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Range finding study: 1 animal/sex/dose
Main study: 5 animals/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 d
- Frequency of observations and weighing: Deaths and overt signs of toxicity were recorded 0.5, 1, 2 and 4h after dosing and subsequently once daily for 14 d. Body weight recorded on Day 0, 7 and 14.
- Necropsy of survivors performed: Yes for the main study; no necropsy in range finding study animals
- Other examinations performed: Behavioural and clinical signs, body weight, gross lesions, mortality and any other toxicological effects

Statistics:

No data

Key result

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities observed in range finding and main study

Clinical signs:

other: No clinical signs observed in range finding and main study

Gross pathology:

No abnormalities were noted at necropsy

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline study according to GLP.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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:

From Mar. 16, 1983 to Mar. 30, 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

other: 40 CFR Part 163.81-2 (EPA Pesticides Programs, proposed guidelines for registering pesticides in the U.S.; hazard evaluation: humans and domestic animals, acute dermal toxicity study)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton-Dutchland, Inc., Denver, Pennsylvania
- Age at study initiation: Young adults
- Weight at study initiation: Males: 2.5 to 2.9 kg, Females: 2.7 to 3.4 kg
- Housing: Individually housed; suspended, stainless steel cages
- Diet: Purina Lab Rabbit Chow HF (#5326), ad libitum
- Water: Automatic watering system, Municipal water supply (Elizabethtown Water Co.), ad libitum
- Acclimation period: 36 d

ENVIRONMENTAL CONDITIONS
- Temperature: 15.55 - 21.11 °C
- Photoperiod: 12 h dark / 12 h light

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: On the day prior to dosing (approximately 18 h), the hair of each rabbit was closely clipped from the trunk (dorsal and ventral surface and sides from scapular to pelvic area) with an electric clipper, so as to expose at least 20% of the body surface area. Just prior to dosing, using a hypodermic needle with the point filed off, the skin of all the animals was abraded longitudinally every 2 or 3 centimeters over the area of exposure. Abrasions were deep enough to penetrate the stratum corneum, but not so deep as to disturb the dermis or produce bleeding.
- Type of wrap: A layer of 8-ply gauze was wrapped around the animal to cover the application site. The animal was then wrapped in an impervious plastic sleeve, designed to contain the test material without leakage or undue pressure. The sleeve was secured with masking tape and Elizabethan collars were placed on all animals.

REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 1.8 mL/kg bw (2000 mg/kg bw)

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Five

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 d
- Viability check: Twice daily
- Observations of pharmacologic and toxicologic signs: Approximately 1, 2, and 4 h after dosing and daily thereafter for 14 d.
- Body weights: Pre-test, at the time of clipping (weights used for calculation of doses); pre-dose (just prior to dosing); Days 7 and 14
- Evaluation of skin irritation: Observations for erythema and edema or other evidence of irritation or injury were made approximately 30 min. after re moval of the occlusive wrapping. Draize scoring scale was used (Draize, 1959).
- Necropsy of survivors performed: Yes, all animals surviving at termination of the observation period (Day 14) were killed by an intravenous overdose of sodium pentobarbital and examined grossly.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: All ten animals exhibited decreased food consumption on day 2 and a few continued to exhibit this finding on day 3. One male was noted to have a swollen scrotum from day 2 through 5. Other signs (nasal or ocular discharge, fecal staining) were noted spora

Gross pathology:

Except for the presence of necrosis and eschar at the dose site in five animals, observations made at necropsy were similar to those seen in control animals in the testing laboratory or were considered to represent normal physiological variations.

Other findings:

- Dermal observations: Moderate to severe erythema accompanied by moderate edema was exhibited in seven of the ten animals 24 h after dosing. One male and two females exhibited well-defined erythema and slight or severe edema. Small areas of necrosis were seen in most animals from day 2, with subsequent eschar formation and exfoliation.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Study equivalent to OECD guideline.

Additional information

There are valid study data available to assess the acute oral and dermal toxicity of the test substance. No study for inhalation toxicity is available.

 

Oral:

A study was conducted (Cytec, 1993) to assess the single dose toxicity of the test substance in Sprague- Dawley rats according to GLP compliant OECD Guideline 401 and EU Method B.1. Groups of 10 Sprague- Dawley rats (5/sex/dose) received a single oral (gavage) dose of 2000 mg/kg undiluted test substance. Parameters evaluated included survival, clinical observations, body weight necropsy findings in all animals after a 14 day observation period. No mortality or clinical signs were observed. All animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy. In conclusion, the single oral median lethal dose (LD50) in Sprague-Dawley rats was calculated to be > 2000 mg/kg bw.

 

Dermal:

A study was conducted to evaluate the acute dermal toxicity of the test substance in rabbits (Cytec, 1983). The study performed was equivalent or similar to OECD guideline 402. Five male and five female New Zealand White rabbits were administered topical applications of 2000 mg/kg bw to the abraded skin. The tests were occluded for 24 hours. All animals were observed twice daily for viability throughout the study. Observations for erythema and edema or other evidence of irritation or injury were made approximately 30 minutes after removal of the occlusive wrapping and scoring was done using the Draize scale. Animals were sacrificed on day 14 and a gross post-mortem examination was performed. No mortality was reported. No change in weight occurred except for one animal which exhibited a slight weight loss on days 7 and 14. Moderate to severe erythema accompanied by moderate edema was exhibited in seven of the ten animals 24 h after dosing. One male and two females exhibited well-defined erythema and slight or severe edema. Small areas of necrosis were seen in most animals from day 2, with subsequent eschar formation and exfoliation. All ten animals exhibited decreased food consumption on day 2 and a few continued to exhibit this finding on day 3. One male was noted to have a swollen scrotum from day 2 through to day 5. Other signs (nasal or ocular discharge, fecal staining) were noted sporadically, generally in a few animals. In conclusion, the dermal median lethal dose (LD50) of the test substance as determined to be > 2000 mg/kg bw in rabbits.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008

The available data for acute toxicity are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on this data, the substance is not considered to be classified for acute toxicity under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.