Allyl (3-methylbutoxy)acetate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

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)

Version / remarks:

Adopted on 09 October 2017

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Allyl (3-methylbutoxy)acetate

EC Number:

266-803-5

EC Name:

Allyl (3-methylbutoxy)acetate

Cas Number:

67634-00-8

Molecular formula:

C10H18O3

IUPAC Name:

allyl (3-methylbutoxy)acetate

Test material form:

liquid

Test animals

Species:

rat

Strain:

other: Rattus norvegicus

Sex:

female

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

A range finding study using 1 female rat at dose rate of 200 mg/Kg b.w. was carried out in order to establish the dose levels for the main study. Seventeen hours prior to the treatment, around 10% dorsal skin area of each rat was clipped free of hair, without any abrasion. The appropriate amount of the test item was applied uniformly over the fur clipped area of each rat.

After the application, the test item was held in contact with the skin for a period of
24 hours, using a gauze dressing (Make: Liv Medica Products Pvt Ltd; Batch No: S0360617; Expiry: May 2022) and bandaged with non-irritating adhesive tape (Make: 3M India Limited; Batch No: R06160302; Expiry: June 2021). After 24 hours, the residual test item was wiped gently from the skin using cotton soaked in distilled water. Animals were individually caged and neck collar was used to prevent the ingestion of the test item from the application site. No mortality was observed over a period of 72 hours in the range finding study at 200 mg/Kg b.w., 1000 mg/Kg b.w and 2000 mg/Kg b.w. and therefore, main study using 2 female rats at the dose of 2000 mg/Kg b.w. was conducted.

Duration of exposure:

24h

Doses:

Range finding: 200, 1000, 2000 mg/Kg b.w
Main study: 2000 mg/Kg b.w

No. of animals per sex per dose:

range finding: 1 female / dose
main study: 2 females / dose

Control animals:

not required

Details on study design:

Step Study Dose (mg/Kg) Number of animals Number of moribund or dead animals Subsequent action
1 Range finding study 200 1 female 0 Proceeded to Step 2
2 Range finding study 1000 1 female 0 Proceeded to Step 3
3 Range finding study 2000 1 female 0 Proceeded to Step 4
4 Main Study 2000 2 females 0 Further testing not required
Animals were observed at 25 min after application and 45 min, 1 h, 2h, 3h, 4h, 5 h, 6h, 7 h, 8h, 9h, 10h, 13 h, 16 h, 19 h, 22h, 24 h and periodically for a total of 14 days. In addition to that the skin reactions were visually scored at 24 h, 48 h and 72 h after removal of test chemical using Draize criteria.

Statistics:

na

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality or morbidity were observed in any of the animals used in this study.

Clinical signs:

In range finding study (200 mg/kg and 1000 mg/Kg), all animals showed signs of nasal irritation immediately after application. Animals were normal after 5 h of application. At 24 h observation, all animals were found normal.
At 2000mg/kg b.w dose, both in range findings and main study, all the animals showed signs of nasal irritation immediately after application and has staggering gait from 1 h to 2 h. Animals were dull, depressed with decreased motor activity from 2 h to 6 h. Animals became normal after 7th h. At 24 h observation, all animals were found normal.

Body weight:

All the animals showed an increase in body weight at the end of the experiment.

Gross pathology:

No gross and histopathological examination were found necessary in this study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results obtained and in line with OECD 402 the acute dermal LD50 of the given test item Allyl Amyl Glycolate (Batch No. AAG-TEST 1) is greater than 2000 mg/Kg b.w.
CLP criteria not met.

Executive summary:

Based on the results obtained and in line with OECD 402 the acute dermal LD50 of the given test item Allyl Amyl Glycolate (Batch No. AAG-TEST 1) is greater than 2000 mg/Kg b.w.

CLP criteria not met.

Acute dermal toxicity of the test itemAllylAmyl Glycolate(Batch No. AAG-TEST 1), following single dermal application was evaluated in female (nulliparous and non-pregnant) Wistar rats.

Since the test item is a colourless liquid it was used as such without any dilution. In order to establish the dose levels for the main study, a range finding study was initiated using 1 female rat at the dose of 200 mg/Kg b.w. The test item was applied uniformly over the fur clipped dorsal area of the rat (10% of the total body surface area). After application, the test item was held in contact with the skin with gauze dressing which was wrapped with non-irritating tape for a period of 24 hours. Animals were maintained in an individual cage with appropriate gauze dressing and neck collar in order to avoid oral ingestion of the test chemical from the test sites.After 24 hours, the residual test item was wiped gently from the skin using distilled water soaked cotton. Since no mortality was observed in 200 mg/kg b.w. dose, based on OECD 402, a higher dose of 1000 mg/kg b.w. & 2000 mg/kg b.w. was evaluated using the same procedure as before. However, a period of 72 h was allowed between the testing of each animal.

There was no mortality in the range finding study at the dose levels of 200 mg/kg b.w, 1000 mg/kg b.w and 2000 mg kg b.w and therefore, main study using 2 female rats at the dose of 2000 mg/Kg b.w. was conducted.

Step	Study	Dose (mg/Kg)	Number of animals	Number of moribund or dead animals	Subsequent action
1	Range finding study	200	1 female	0	Proceeded to Step 2
2	Range finding study	1000	1 female	0	Proceeded to Step 3
3	Range finding study	2000	1 female	0	Proceeded to Step 4
4	Main Study	2000	2 females	0	Further testing not required

Animals were observed at 25 min after application and 45 min, 1 h, 2h, 3h, 4h, 5 h, 6h, 7 h, 8h, 9h, 10h, 13 h, 16 h, 19 h, 22h, 24 h and periodically for a total of 14 days. In addition to that the skin reactions were visually scored at 24 h, 48 h and 72 h after removal of test chemical using Draize criteria. The mean score of skin reactions are follows,

Animal number	Range finding study			Main study
	1	2	3	4	5
	T	T	T	T	T
Erythema and Eschar formation	0	0	0	0	0
Oedema formation	0	0	0	0	0

   T: Treated

In range finding study (200 mg/kg and 1000 mg/Kg), all animals showed signs of nasal irritation immediately after application. Animals were normal after 5 h of application. At 24 h observation, all animals were found normal.

At 2000mg/kg b.w dose, both in range findings and main study, all the animals showed signs of nasal irritation immediately after application and has staggering gait from 1 h to 2 h. Animals were dull, depressed with decreased motor activity from 2 h to 6 h. Animals became normal after 7^thh. At 24 h observation, all animals were found normal.

No mortality and morbiditywereobserved in any of the animals used in this study.
All the animals showed anincreasein body weight at the end of the experiment.