Cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked

Endpoint summary

Description of key information

No acute toxicity tests are available for the inhalation route of exposure. A data waiver is claimed.
Cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked is of low oral and dermal acute toxicity  with an oral LD50 (rat) of > 2000 mg/kg bw (Hüls AG, 1998) and a dermal LD50 (rat) of > 2000 mg/kg bw (LPT, 2012).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998-02-16 to 1998-03-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS: 
- Strain: Cpb/Win:WU (SPF)
- Source: Harlan Winkelmann GmbH, Borchen (Germany)
- healthy, young adult animals
- Controls: no
- Fasting period before study: 16 hours
- Diet: ad libitum, R10 special diet for rats, SSniff R
- Water: ad libitum, tab water
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30 - 70 %
- Photoperiod (hrs dark / hrs light): 12 hours artificial light, 12 hours dark
- Air changes (per hr): 15 per hour

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

ADMINISTRATION: 
- test compound was grinded and suspended in corn oil
- 20 g/100ml
- Doses per time period: single dose (gavage)
- Volume administered : 10 ml/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

EXAMINATIONS: 
- Mortality, clinical signs: soon after dosing and at frequent intervals for day 0, than once daily for next 2 weeks
- Body weights: days 0, 7, and 14
- Post dose observation period: 14 days
- Macroscopic examination: directly after exitus (animal that died) / day  14 (surviving animals)

Statistics:

not required

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred. 

Clinical signs:

other: No signs of systemic reaction to treatment.

Gross pathology:

NECROPSY FINDINGS: Macroscopical examination revealed no abnormalities.

Other findings:

no other findings

no further remarks

Conclusions:

According to this study the LD50 value (oral) was estimated to be > 2000 mg/kg bw in rats for the test item.

Executive summary:

In an acute oral toxicity study (limit test) according OECD 401 a single dose of 2000 mg/kg  test item was applied to three male and female Wistar rats.

The observation period was 14 days.

There were no deaths and no signs of systemic reaction to treatment, body weight development was normal.

Macroscopical examination revealed no abnormalities at the end of the observation period.

Under conditions of this study the LD50 value (oral) is above 2000 mg/kg bw in Wistar rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The study is valid without restriction (Klimisch score 1).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

According to REACH Annex VIII (Column 2 of section 8.5.3) acute inhalation study is not needed, because inhalation of the substance is unlikely during use or/and production and skin contact is considered to be the relevant route of exposure during use or/and production.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2011-09-26 to 2011-10-24

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

other: Rattus norvegicus

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Strain: Rattus norvegicus CD / Crl: CD(SD)
- Sex, age and body weight range
5 males, 8 weeks old, 200 - 213 g
5 females, 9 weeks old, 200 - 220 g
- Controls: no
- Fasting period before study: 16 hours
- Diet: ad libitum, R10 special diet for rats, SSniff R
- Water: ad libitum, tab water
- Acclimation period: at least 5 days
- Housing: during the 14-day observation period animals were kept singly in MAKROLON cages (type III plus)
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 55 +/- 15 %
- Photoperiod (hrs dark / hrs light): 12 hours artificial light, 12 hours dark
- Air changes (per hr): 15 per hour

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

- Method of administration:
The intact dorsal skin of the animals was shaved free of hair with a shaver . The site was situated on the animal´s back between the fore and hind
extremities and had an area of at least 5 cm x 6 cm (approx. 1/10 of body surface).
The test patch was occlusive. The test item was held in contact with the skin with 8 layers of gauze. The gauze was covered with a plastic sheet and
secured with adhesive plaster strips on the application site for 24 hours.

Duration of exposure:

24 hours

Doses:

- 2000 mg/kg bw,
- administration volume 10 ml/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

EXAMINATIONS: 
- Clinical signs:  before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration
- Mortality: at least once daily
- Body weights: days 0, 7, and 14
- Post dose observation period: 14 days
- Macroscopic examination:  day  14 

Statistics:

not required

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no mortalities

Mortality:

No mortality was observed at 2000 mg/kg

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

Macroscopic examination did not reveal any changes.

Other findings:

No other findings

No further information

Conclusions:

Based on the results of this study the dermal LD50 of test item was estimated to be > 2000 mg/kg in male and female rats.

Executive summary:

In this experiment the test item was examined for acute toxicity after a single dermal application to rats.

One dose level of 2000 mg/kg b.w. was employed (limit test).

Under the present test conditions, a single dermal application of 2000 mg test item/kg b.w. to rats did not reveal any clinical signs of toxicity. No influence on animal behaviour or premature death was noted. The body weight gain was not influenced by the test item administration. No skin reactions were observed at the application site.The macroscopic examination did not reveal any changes.

Based on the results of this study the dermal LD50 of test item was > 2000 mg/kg in male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The study is valid without restriction (Klimisch score 1).

Additional information

No acute toxicity tests are available for the inhalation route of exposure. A data waiver is claimed. Cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked is of low oral and dermal acute toxicity with an oral LD50 (rat) of > 2000 mg/kg bw (Hüls AG, 1998) and a dermal LD50 (rat) of > 2000 mg/kg bw (LPT, 2012).

Justification for selection of acute toxicity – oral endpoint
Only one study available.

Justification for selection of acute toxicity – dermal endpoint
Only one study available.

Justification for classification or non-classification

Based on the results of the acute oral and dermal studies and according to the criteria of EC Regulation 1272/2008 cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, acetone oxime-blocked has a very low acute toxicity if swallowed or if it comes in contact with skin. Therefore, the test substance must not be classified.