Diallyl hexahydrophthalate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 December 2017 to 29 December 2017 (Experimental start to experimental completion)

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

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diallyl hexahydrophthalate

EC Number:

237-580-1

EC Name:

Diallyl hexahydrophthalate

Cas Number:

13846-31-6

Molecular formula:

C14H20O4

IUPAC Name:

1,2-bis(prop-2-en-1-yl) cyclohexane-1,2-dicarboxylate

Test material form:

liquid

Remarks:

Colourless

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source of test material: Osaka Soda Co Ltd., Japan
- Lot/batch No.of test material: 40201
- Expiration date of the lot/batch: 26 January 2019
- Purity test date: 26 September 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature, protected from light
- Stability under test conditions: Assmued stable for the duration of the test
- Solubility and stability of the test substance in the solvent/vehicle: Not applicable, test item administered as supplied.
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: Not applicable, no vehicle used. Test item was administered as supplied.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None, test item used as supplied.

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI Wistar rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld, Germany
- Males: yes
- Females (if applicable): yes, nulliparous and non-pregnant
- Age at study initiation: Young adult rats
- Weight at study initiation: 241g - 270g
- Fasting period before study: Not specified
- Housing: Individual caging (Type II. polypropylene/polycarbonate)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 or 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1 - 25.0°C
- Humidity (%): 30-48%
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

IN-LIFE DATES: From: To: 13 December 2017 to 29 December 2017 (Experimental start to experimental completion)

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back of each animal
- % coverage: Approximately 10% area of the total body surface
- Type of wrap if used: semi-occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of 24 hour treatment, washed with water at body temperature
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Test item administered as a single (limit) dose at 2000 mg/kg bw (without vehicle) as supplied.

Duration of exposure:

24-hour

Doses:

Single (limit) dose of 2000 mg/kg bw

No. of animals per sex per dose:

5 animals / sex

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were performed on day of treatment at 1 and 5 hours after application of test item and once each day for 14 days thereafter. Body weights were recorded on Day 0 prior to test item administration and on days 7 and 14 (prior to necropsy)
- Necropsy of survivors performed: yes, macroscopic examination was performed on all animals. All animals were anaesthetised with pentobarbital sodium and exsanguinated. Following confirmation of death, after examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed. All macroscopic changes were recorded.

- Other examinations performed: Observations included skin and fur, eyes and mucous membranes, the respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was given to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. Gross macroscopic examination was performed on all animals at necropsy at the end of the 2-week observation period.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

no indication of skin irritation up to the relevant limit dose level

Mortality:

The test item did not cause mortality at the dose level of 2000 mg/kg bw

Clinical signs:

Systemic Clinical Signs: No systemic clinical signs were noted in any animal throughout the study

Local Dermal Signs: No adverse local dermal signs were observed after treatment with the test item or during the 14 days observation period.

Body weight:

One out of 10 animals had body weight loss (-3g) between Day 0-7. This bodyweight loss was temporary and returned to normal range later in the study. There were no treatment related effects on body weight or body weight gain during the observation period.

Gross pathology:

There was no evidence of any gross macroscopic changes at a dose level of 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) of the test item MDAC was found to be greater than 2000 mg/kg body weight in male and female Crl:WI rats.
According to the GHS criteria. MDAC can be ranked as "Unclassified" for acute dermal exposure.

Executive summary:

An acute dermal toxicity study was performed with the test item MDAC in male and female Crl:WI Wistar rats, in compliance with OECD Guideline No. 402, Commission Regulation (EC) No 440/2008, B.3 and OPPTS 870.1200 [1 -3].

A limit test was carried out at 2000 mg/kg body weight (bw) in both sexes (5 rats/sex). The test item was applied as a single dermal 24 -hour exposure followed by a 14 -day observation period.

Clinical observations were performed on all animals at 1 and 5 hours after dosing and daily for 14 days thereafter. Body weight was measured on Day 0 (prior to dosing) and on Days 7 and 14 (before necropsy). Gross macroscopic examination was performed on all animals at necropsy at the end of the 2 -week observation period (Day 14).

Application of MDAC at 2000 mg/kg bw had no effect of mortality, no observable systemic clinical signs, no adverse local dermal signs, and no treatment related effects on body weight and body weight gain. No gross macroscopic changes were observed at necropsy.

The study concluded that the acute dermal median lethal dose of MDAC was >2000 mg/kg bw in male and female Crl:WI rats. According to GHS criteria, MDAC can be ranked as "Unclassified" for acute dermal exposure.