Reaction mass of allyl (2-methylbutoxy)acetate and allyl (3-methylbutoxy)acetate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6th February 2018 - 3rd May 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of allyl (2-methylbutoxy)acetate and allyl (3-methylbutoxy)acetate

EC Number:

916-328-0

Molecular formula:

C10H18O3

IUPAC Name:

Reaction mass of allyl (2-methylbutoxy)acetate and allyl (3-methylbutoxy)acetate

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: O’Laughlin (Nantong) Fine Chemicals Co., Ltd.; NTA375
- Expiration date of the lot/batch: Sep 25, 2020
- Purity: CAS No. 67634-00-8: 79.45 %; CAS No.: 67634-01-9 20.28 %

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Store in cool place. Keep container tightly closed in a dry and well-ventilated place.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeding farm VELAZ s.r.o., Lysolajské údolí 15/53, 165 00 Prague 6, Czech Republic, RČH CZ 11760500
- Females (if applicable) nulliparous and non-pregnant: Yes
- Weight at study initiation: 211-236 g
- Housing: Animal room with monitoring conditions; shavings of soft wood
- Diet: Pelleted standard diet for experimental animals ad libitum
- Water: Drinking tap water ad libitum
- Acclimation period: 21 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30 – 70 %
- Photoperiod (hrs dark / hrs light): 12-hour light/12 hour dark

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: About 6 x 6 cm on the back of animals (shaved)
- % coverage: Approx. 10 % of the body surface
- Type of wrap if used: Gauze and held in contact by plaster (strapping)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No

Duration of exposure:

24 hrs

Doses:

Range finding study: 1000 mg/kg bw
Main study: 200, 1000 mg/kg bw/day

No. of animals per sex per dose:

Range finding study: 1 female
Main study: 2 females per dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: After application the animals were observed individually:
-the first day: three times (30 minutes, 3 and 6 hours after application)
- the second day: twice (in the morning and in the afternoon) and daily thereafter for 14 days
- Frequency of observations and weighing: The animals were weighed at the start of the study (before application), at 8th day and at the end of experiment (15th day).
- Necropsy of survivors performed: All test animals surviving to the end of study were sacrificed on the 15th day by diethyl ether narcosis and gross necropsy was carried out. Nutritional state, body surface, body foramina, thoracic, abdominal and cranial cavity were evaluated
- Other examinations performed: Observations included changes in skin and fur, eyes, visible mucous membranes, behaviour of animals, somatomotor activity, reactions to stimuli, and presence of lacrimation, salivation and discharge from nostrils, function of respiratory, digestive and urogenital system

Results and discussion

Preliminary study:

The test item at the dose level 1000 mg/kg bw caused the death of the animal. Clinical signs of intoxication noted as apathy, decreased reaction to stimuli and red discharge from nostrils were observed 6 hours after administration of the test item. The following morning, the animal was found dead. Red-stained fur around the urethra outflow was recorded. Red-stained content of the small intestine and congested small intestine were observed. Based on these results, the main study with two females was started with the dose of 200 mg/kg bw.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 1 000 - <= 2 000 mg/kg bw

Mortality:

No death of animals was recorded at the dose level 200 mg/kg bw. One of the two females at the dose level 1000 mg/kg bw died during the main study.

Clinical signs:

other: Clinical signs of toxicity noted as apathy, decreased reaction to stimuli, bradypnoea, piloerection, red discharge form nostrils, dark red-stained urine were observed in females at the dose level 1000 mg/kg bw. No clinical signs of toxicity were recorded

Gross pathology:

During the pathological examination, changes as dilatation of the small intestine, congestion of the intestine and dark red-stained urine were diagnosed in one female dosed by 1000 mg/kg bw. No macroscopic findings were recorded in females at the dose level 200 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

In an acute dermal toxicity study in rats, the LD50 for allyl amyl glycolate was >1000 mg/kg bw - ≤2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study (18 -163) 2 female Wistar rats were dermally exposed (semi-occlusive) to allyl amyl glycolate at doses of 200 and 1000 mg/kg bw for 24 hours. Animals were then observed for 14 days.

Dermal LD50 (Females) = >1000 mg/kg bw - ≤2000 mg/kg bw.

No death of animals was recorded at the dose level 200 mg/kg bw. One of the two females at the dose level 1000 mg/kg bw died. The body weight gain was adequate to species, sex and age of animals except very little body weight gain in one animal at 200 mg/kg bw. No clinical signs of toxicity were recorded in females at the dose level 200 mg/kg bw. Clinical signs of toxicity noted as apathy, decreased reaction to stimuli, bradypnoea, piloerection, red discharge form nostrils, dark red-stained urine were observed in females at the dose level 1000 mg/kg bw. No macroscopic findings were recorded in females at the dose level 200 mg/kg bw. During the pathological examination, changes as dilatation of the small intestine, congestion of the intestine and dark red-stained urine were diagnosed in one female dosed by 1000 mg/kg bw.

This acute dermal study is classified as acceptable. It does satisfy the guideline requirement for an acute oral study (OECD 402) in the rat.