Diallyl isophthalate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23 March to 26 June 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

DAIM

IUPAC Name:

DAIM

Test material form:

liquid

Details on test material:

Name of test material (as cited in study report): Daiso DAPTM 100 Monomer (DAIM)
- Physical state: Viscous liquid, colourless and transparent
- Molecular formula (if other than submission substance):
- Molecular weight (if other than submission substance):
- Analytical purity: 99.9%
- Lot/batch No: 24112
- Storage: Refrigerated in a tight container in the dark (3.1-6.9°C). On receipt stored at room temperature (18.4-20.5°C).
- Expiry date: 1st March 2020

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

Source: Hino Breeding Centre, Charles River Laboratories Japan, Inc
Animals were quarantined for a minimum of 5 days with acclimatisation (from receipt to the day before dosing) 5, 7 and 12 days respectively for groups 1, 2 and 3. Group 4 animals were not used.
Age at study initiation: All group animals 9 weeks at dose administration
Weight at study initiation: Group 1 (194.2-204.6g), Group 2 (205.8-213.1g), Group 3 (193.9-209.5g)
Fasting: Animals were fasted ca. 19 hours (pre-dose) and 3 hours (post-dose)
Housing: One animal housed per cage (W226 x D346 x H198). Stainless steel cage and feeders changed at dose administration, cage racks at animal grouping and cage trays weekly.
Feed: Autoclave-sterilised pellet diet (CRF-1 Oriental Yeast Co., Ltd) ad libitum. Lot analysis performed, contaminants were within acceptable limits.
Water: Well water mixed with NaCLO (free residual chlorine concentration at 2ppm) ad libitum. Analysis performed twice yearly and confirmed within acceptable limits.
Environmental enrichment: Autoclaved alumina balls exchanged on the day of administration.
Temperature: 22.5-23.3°C
Humidity: 49.5-61%
Air changes: 10-20 p/h
Lighting: 12 hour light/dark 07:00 to 19:00
In life phase: 1st April (dosing expt 1) – 17 April (necropsy expt 2)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Dosing solutions: 30 mg/mL (groups 1 & 2) 200 mg/mL (group 3). Starting dose set at 300 mg/kg due to no toxicological data or information on a similar test substance known

Doses:

Group: 1 (300 mg/kg) 2: (300 mg/Kg) 3: (2000 mg/kg)

No. of animals per sex per dose:

Three females

Control animals:

no

Details on study design:

Based on the step wise procedure in accordance with OECD 423 Guideline requirements
Duration of observation period: 14 days
Frequency of observations: 0.5, 1, 3 and 5 hours post dose on administration day. Thereafter once daily for 14 days unless clinical observations necessitated increased frequency based on clinical observations
Frequency of bodyweight: On day 1 before dosing and days 2, 4, 8 and 15
Necropsy of survivors performed: Yes
Other examinations performed: clinical observations, bodyweight and gross pathology (macroscopic examination)

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

500 mg/kg bw

Based on:

test mat.

Remarks on result:

other: Estimated

Mortality:

No mortality was observed in either group 1 or 2 animals dosed at 300 mg/kg. In group 3 animals dosed at 2000 mg/kg, two rats died, one on day 2 and one on day 3, the remainder was moribund on Day 3.

Clinical signs:

In group 1 (300 mg/kg) no clinical signs were observed in group animals.
In group 2 (300 mg/kg) a mucous stool was observed in a single animal 3-hours post dose on Day 1.
In group 3 (2000 mg/kg), one animal showed slight salivation 0.5 hours post-dose with slight decrease in locomotor activity observed at 0.5 and 3.0 hours. No clinical signs were present 5 hours. The following morning (Day 2), slight decreased locomotor activity was again present. In the afternoon moderate decreased locomotor activity, bradypnea, hypothermia, pale skin and slight lacrimation were observed which also persisted throughout day 3 where the animals was judged moribund.

One animal showed slight lacrimation 0.5 and 1.0 hour post-dose with slight decrease in locomotor activity observed at 0.5 and 3 hours. No clinical signs were present 5 hours post-dose, however they had returned on of the morning Day 2. In the afternoon moderate decrease locomotor activity (moderate), bradypnea, hypothermia, pale skin and slight lacrimation were observed. The animal died the following morning (Day 3).

One animal showed slight decrease in locomotor activity 3 hours post-dose. No clinical signs were present at 5 hours, however the animal died the following morning (Day 2).

Body weight:

In group 1 a decrease in bodyweight or suppression of bodyweight gain was observed in a single animal between days 1 and 2. This effect was observed in all group 2 animals. In both groups no effects were observed on Day 3.

In group 3, suppressed bodyweight gain was observed in a single animal with no abnormalities observed in the remainder between days 1 and 2.

Gross pathology:

In all animals from groups 1 and 2 no abnormalities were observed. In group 3 animals, no abnormalities were present in the two animals found dead on days 2 and 3. In the moribund animal a dark reddish change to the duodenum and edema of the lungs (and bronchus) was observed. Hyposthenia following haemorrhage of the duodenum and pulmonary edema was judged to be the cause of the moribundity.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

No clinical observations of concern were observed in groups 1 and 2 dosed at 300 mg/kg. In group 3, two animals died and one was judged moribund. Based on the step wise procedure in accordance with OECD 423, DAIM was GHS/CLP categorised as category 4, with its approximate LD50 estimated to be 500 mg/kg.