1,2,3,6-tetrahydro-3-methylphthalic anhydride

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1993-08-04 to 1993-08-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1981

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

84/449/EEC

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tetrahydromethylphthalic anhydride

EC Number:

234-290-7

EC Name:

Tetrahydromethylphthalic anhydride

Cas Number:

11070-44-3

IUPAC Name:

3a-methyl-3a,4,5,6-tetrahydro-2-benzofuran-1,3-dione

Details on test material:

- Name of test material (as cited in study report): P0314 (Methyltertrahydrophtalic anhydride/NT)
- Physical state: colourless slightly viscous liquid
- Analytical purity: 99.9 %
- Lot/batch No.: 93/307
- Storage condition of test material: room temperature in clear glass jar
- Molecular formula (if other than submission substance): C9 H10 O3
- Molecular weight (if other than submission substance): 166.18
- Smiles notation (if other than submission substance): O=C(OC(=O)C1CC=C(C2)C)C12
- InChl (if other than submission substance): 1/C9H10O3/c1-5-2-3-6-7(4-5)9(11)12-8(6)10/h2,6-7H,3-4H2,1H3
- Structural formula attached as image file (if other than submission substance): see Fig. (11070-44-3 structure.jpg)

Test animals

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.
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 10 - 14 weeks
- Weight at study initiation: males - 234-255 g; females - 207-237 g
- Fasting period before study: n/a
- Housing: Individually during the 24-hour exposure period and in groups of up to five, by sex, for the remainder of the study.
- Diet: R&M No. 1, Special Diet Services Limited, Witham, Essex, U.K., ad libitum
- Water: Municipal supply, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22°C
- Humidity (%): 50-56%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1993-08-04 To: 1993-08-18

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: ca. 5 x 4 cm
- % coverage: ca. 10%
- Type of wrap if used: semi-occluded

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes - distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied: 1.68 mL/kg bodyweight giving a dose level of 2000 mg/kg body weight
- Constant concentration used: yes - undiluted
- For solids, paste formed: yes/no

Duration of exposure:

24 h

Doses:

2000 mg/kg bw (1.68 mL/kg bw)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed for deaths or overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Examined for any dermal reactions after removal of the dressings and subsequently once daily for the remainder of the study. Bodyweight recorded Days 0, 7 and 14.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:

no preliminary study

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the study. Dermal Reactions: Very slight to well-defined erythema was noted at the treatment sites of all animals one day after dosing with very slight erythema in all females two days after dosing. Haemorr

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

none

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) of the test material, tetrahydromethylphthalic anhydride, in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bw.

Executive summary:

The study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 402 "Acute Dermal Toxicity" referenced as Method B.3 in Commission Directive 84/449/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

A group of ten animals (five males and five females) was given a single 24-hour, semi-occluded dermal application to intact skin at a dose level of 2000 mg/kg bw. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination.

There were no deaths. No signs of systemic toxicity were noted during the study. Very slight to well-defined erythema was noted at the

treatment sites of all animals. Other skin reactions noted were haemorrhage of the dermal capillaries and crust formation. Treatment sites appeared normal two to five days after dosing. All animals showed expected gain in bodyweight during the study. No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight.