Reaction products of 3-aminomethyl-3,5,5-trimethylcyclohexylamine with 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2007-10-03 to 2007-12-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2001

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

92/69/EEC

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:

Reaction products of 3-aminomethyl-3,5,5-trimethylcyclohexylamine with 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

EC Number:

614-657-1

Cas Number:

68609-08-5

Molecular formula:

C41H68N4O4

IUPAC Name:

Reaction products of 3-aminomethyl-3,5,5-trimethylcyclohexylamine with 2,2'-[(1-methylethylidene)bis(4,1-phenyleneoxymethylene)]bisoxirane

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (Europe) Laboratories Inc. TOXI COOP Ltd. 1103 Budapest, Cserkesz u. 90.
- Age at study initiation: Young adult rats
- Weight at study initiation: Male: 252 - 283 g; Female: 216 - 239 g
- Fasting period before study: None
- Housing: Individual caging (1 animal/cage); Type II polypropylene/polycarbonate
- Diet: Animals received ssniff® SM R/M-Z+H "Autoclavable complete feed for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany and tap water from the municipal supply, ad libitum.
- Acclimation period: 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 -24 °C
- Humidity (%): 38 - 58 %
- Air changes (per hr): 8 - 12 air exchanges/hour by central air-condition system
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: Test item was pulverized and moistened with water

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 10 per cent of the total body surface
- % coverage: appr. 10
- Type of wrap if used: semi occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: water at body temperature
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount applied: single dose of 2000 mg/kg bw
- For solids, paste formed: yes, with water

Duration of exposure:

24 hrs

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

Males: 5; 2000 mg/kg bw;
Females: 5; 2000 mg/kg bw;

Control animals:

no

Details on study design:

Observations: Animals were observed for a 14-day post-treatment period. Clinical examinations, body weight assessment and gross necropsy were conducted.

Clinical Examination: A careful individual clinical examination was made on the day of treatment 1 h and 5 h after the administration of the test item, and once each day for 14 days thereafter. Individual observations were performed on the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern.

Weight Assessment: The body weight of each animal was recorded on day 0 (beginning of the experiment), on day 7 and on day 14 with a precision of 1 g.

Pathology: On day of the last clinical observation, all animals were exsanguinated under carbon dioxide anaesthesia and gross necropsy was performed. 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 gross pathological changes were recorded for each animal on post mortem record sheets.

Evaluation of Results: The method used allows assigning an LD50 value, according to the OECD Guidelines for Testing of Chemicals, No. 402, and B.3. 92/69/EEC.
Individual animal data were provided and summarised in tabular form, showing for each dose group the number of animals used.
Clinical observations were noted individually and in summary tables.
Body weight changes were summarised in tabular form.
Necropsy findings were described and summarised in tabular form.

Statistics:

No statistics performed

Results and discussion

Preliminary study:

No preliminary study was performed

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male Female
Dose level (mg/kg bw): 2000 2000
Number of animals treated: 5 5
Number of dead animals: 0 0

Clinical signs:

other: There were no clinical signs. The behaviour and physical condition of animals were considered to be normal. 2000 mg/kg bw of the test item caused slight to marked erythema (5/5 male, 5/5 female), erosion (1/5 female) and sloughing (3/5 male, 5/5 female) o

Gross pathology:

No macroscopic alterations due to the effects of the test item were found. Gross necropsy revealed pinprick-sized haemorrhages (5/5 male, 2/5 female) and reddish mottled colour (1/5 female) in the lungs due to the method of anaesthesia and exsanguinations, which are also observable in untreated animals after anaesthesia.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the present study, a single 24-hour dermal administration of 2000 mg/kg bw of the test item, the test item caused erosion, erythema and sloughing on the treated skin, which recovered within 2 - 13 days. Mortalities were not observed, neither in male nor in female CRL:(WI)BR rats. The acute dermal LD50 value of the test item is greater than 2000 mg/kg bw in male and female CRL: (WI) BR rats.

Executive summary:

The acute dermal toxicity study (Limit Test) with the test item was performed in compliance with OECD guideline No.: 402 and method B.3. 92/69/EEC. A limit test was carried out at 2000 mg/kg bw dose level. Five male and five female CRL:(WI)BR rats were treated with a dose of 2000 mg/kg bw. The test item was applied once in its original form by dermal route and held in contact with the skin for a 24-hour period. The observation period after patch removal continued for 14 days. Clinical observations were made one and five hours after the treatment, then once a day. Body weight was measured weekly. Gross necropsy was performed in all animals at the termination of the experiment.

Mortality

No mortality was observed in male and female animals up to the limit dose of 2000 mg/kg bw.

Clinical Observations

There were no clinical signs. The behaviour and physical condition of animals were considered to be normal. 2000 mg/kg bw of the test item caused slight to marked erythema (5/5 male, 5/5 female), erosion (1/5 female) and sloughing (3/5 male, 5/5 female) on the skin after 24-hour exposure. Skin became normal between days 2 and 10 in male animals and between days 8 and 13 in female animals.

Body Weight

The mean body weight and the body weight gain of the male and female animals were considered to be normal during the two-week observation period., similar to the expected values in untreated animals of the same age and strain.

The following table contains the body weight and body weight gain values of control animals of same age and strain.

Male animals: 

	Body weight (g)			Body weight gain (g)
	Day 0	Day 7	Day 14	Day 0 - 7	Day 7 - 14	Day 0 - 14
Mean	264.5	316.6	366.4	52.0	49.8	101.9
Sd	15.0	14.1	15.1	4.9	7.6	8.7
n	21	21	21	21	21	21

Female animals: 

	Body weight (g)			Body weight gain (g)
	Day 0	Day 7	Day 14	Day 0 - 7	Day 7 - 14	Day 0 - 14
Mean	226.7	242.7	251.3	16.0	8.7	24.7
Sd	6.8	7.3	10.2	7.8	5.8	11.1
n	23	23	23	23	23	23

Necropsy

No macroscopic alterations due to the effects of the test item were found. Gross necropsy revealed pinprick-sized haemorrhages (5/5 male, 2/5 female) and reddish mottled colour (1/5 female) in the lungs due to the method of anaesthesia and exsanguinations, which are also observable in untreated animals after anaesthesia.

Under the conditions of the present study, a single 24 -hour dermal administration of 2000 mg/kg bw of test item, the test item caused erosion, erythema and sloughing on the treated skin, which recovered within 2 - 13 days. Mortalities were not observed, neitehr in male nor in female CRL:(WI)BR rats. The acute dermal LD50 value of the test item is greater than 2000 mg/kg bw in male and female CRL:(WI) BR rats.