3-methyl-1,5-pentanediyl diacrylate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 June 2013 - 06 August 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

see below

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Principles of method if other than guideline:

The study was performed in accordance with study plan No. 40081 TAR and subsequent amendment, with the following deviations from the agreed study plan:
. on day 1, females were observed during the first 5 hours after treatment for the recording of the clinical signs, instead of during the first 4 hours after treatment
These deviations were considered not to have compromised the validity or integrity of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-methyl-1,5-pentanediyl diacrylate

EC Number:

264-727-7

EC Name:

3-methyl-1,5-pentanediyl diacrylate

Cas Number:

64194-22-5

Molecular formula:

C12H18O4

IUPAC Name:

3-methyl-5-(prop-2-enoyloxy)pentyl prop-2-enoate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France.
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: the males had a mean body weight of 314 g (range: 304 g to 325 g) and the females 201 g (range: 197 g to 208 g).
- Housing: the animals were housed by five from the same sex and group in polycarbonate cages.
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: a period of 5 days before treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h

IN-LIFE DATES: 09 July 2013 to 26 July 2013

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10% of body surface, dorsal site
- Type of wrap if used: hydrophilic gauze pad + adhesive hypoallergenic aerated semi-occlusive dressing + restraining bandage

REMOVAL OF TEST SUBSTANCE
- Removal of dressing: 24h post-exposure

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.905 mL/kg
- Constant volume: no
- For solids, paste formed: no

Duration of exposure:

one single exposure

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).

Statistics:

no

Results and discussion

Preliminary study:

no

Effect levels

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

other: No clinical signs indicative of systemic toxicity were observed in any animals. Very slight to severe erythema was noted on the application sites of males and females, from day 2 up to day 11 at the latest. Very slight to moderate dryness was observed on

Gross pathology:

There were no test item-related changes at necropsy.
Diffuse red discoloration of the left thymic lobe was observed in one female given 2000 mg/kg. As this observation is commonly seen in the rat, any relationship with the test item was excluded.

Other findings:

no

Any other information on results incl. tables

 Table 1

Sex	Female		Male
Group	Historical control data	1	Historical control data	2
Dose-level (mg/kg)	0	2000	0	2000
Body weight (mean (± SD))
. Day 1	236 (± 8.9)	201 (± 4.8)	362 (± 12.0)	314 (± 8.5)
. Day 8	253 (± 12.0)	215 (± 3.9)	394 (± 15.3)	343 (± 17.2)
. Day 15	273 (± 16.3)	232 (± 4.1)	441 (± 21.5)	389 (± 19.8)
Body weight change (mean (± SD))
. Days 1-8	+17 (± 11.0)	+13 (± 5.5)	+32 (± 9.1)	+28 (± 11.1)
. Days 8-15	+20 (± 7.1)	+17 (± 6.2)	+47 (± 7.5)	+46 (± 4.5)
. Days 1-15	+37 (± 16.3)	+31 (± 6.0)	+79 (± 15.6)	+75 (± 12.2)

SD: standard deviations.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 of the test item was higher than 2000 mg/kg in rats.

Executive summary:

The objective of this study was to evaluate the potential toxicity of the test item following a single dermal application to rats.

This study was conducted in compliance with the OECD guideline No. 402 and the principles of Good Laboratory Practice.

The test item was applied in its original form to the skin of five female then five male Sprague-Dawley rats at the dose-level of 2000 mg/kg. The application site was covered by a semi-occlusive dressing for 24 hours.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. From day 2, any local reactions at the treatment site were also noted. Body weight was recorded on day 1 and then on days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination. Macroscopic lesions were preserved in buffered formalin then destroyed at the finalization of the study reportas no microscopic examination was performed.

No unscheduled deaths occurred during the study and no clinical signs indicative of systemic toxicity were observed in any animals.

Very slight to severe erythema was noted on the application sitesof males and females, from day 2 up to day 11 at the latest. Very slight to moderate dryness was observed on the application sites from day 5 to days 15 at the latest for females and 13 at the latest for males. Scabs on the application site were noted in 3/5 males and 3/5 females starting on day 5, 6 or 8, and up to day 11 at the latest.

These erythema, scabs and dryness were considered test item-related.

Body weight of animals was unaffected by the test item treatment when compared to CiToxLAB France historical control data.

There were no test item-related changes at necropsy.

Fourteen days following a single dermal application of test item at the dose-level of 2000 mg/kg to rats, no test item-related changes were seen at necropsy. The dermal LD50 of the test item was higher than 2000 mg/kg in rats.