Methoxycyclododecane

Endpoint summary

Description of key information

Oral (OECD 425), rat: LD50 > 5000 mg/kg bw (limit test)
Dermal (OECD 402), rat: LD50 > 2000 mg/kg bw (limit test)

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:

10 Nov - 08 Dec 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

(adopted 23 March 2006)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

The department of health of the government of the United Kingdom

Test type:

up-and-down procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Limited, Bicester, Oxon, UK
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 185 - 192 g
- Fasting period before study: overnight
- Housing: individually in suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: 2014 Teklad Global Rodent diet (Harlan Teklad, Bicester, Oxon, UK) , ad libitum
- Water: drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 20 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5.58 mL/kg bw

Treatment of animals was sequential.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

The oral LD50 was calculated by the maximum likelihood method.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths were noted until the end of the observation period.

Clinical signs:

Hunched posture and tiptoe gait were noted in two animals. Signs of systemic toxicity also noted in one animal were ataxia, pilo-erection and dehydration. There were no signs of systemic toxicity noted in one animal.

Body weight:

All animals showed expected gains in bodyweight over the study period.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 value of the test material in the female Wistar strain rat was found to be greater than 5000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 24 February 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

The department of health of the government of the United Kingdom

Test type:

standard acute method

Limit test:

yes

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, Margate, Kent
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation:
- Fasting period before study:
- Housing: individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study
- Diet: Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essesx, UK, ad libitum
- Water: ad libitum
- Acclimation period: minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 25
- Humidity (%): 30 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks of each animal
- % coverage: 10%
- Type of wrap if used: surgical gauze was placed with a piece of self-adhesive bandage


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.21 mL/kg bw

Duration of exposure:

24 hours

Doses:

2000 mg/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: The animals were observed for deaths and overt signs of toxicity 0.5, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: After removal of the dressings and subsequently once daily for 14 days, the test sites were examined for evidence of primary irritation and scored according to the Draize scoring system.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths were noted until the end of the observation period.

Clinical signs:

No clinical signs of toxicity were noted during the study.

Body weight:

All animals showed expected gains in bodyweight over the study period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

Crust formation was noted in two female animals two and three days after dosing. No other signs of dermal irritation were noted. The scores for erythema and edema were 0 throughout the study period.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal LD50 value of the test material in male and female rats was found to be greater than 2000 mg/kg bw. Besides, crust formation in two female animals two and three days after dosing, no other signs of dermal irritation were noted throughout the study period (scores for eryhema and edema = 0).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1). This study is not a standard information requirement set out in Annex VII of Regulation (EC) No 1907/2006 and is thus considered as additional information.

Additional information

Justification for selection of acute toxicity – oral endpoint
The reliable GLP compliant OECD Guideline study was chosen. In a OECD 425 and GLP compliant study, the acute oral LD50 value of the test material in the female Wistar strain rat was found to be greater than 5000 mg/kg bw. No mortalities were observed.

The rat study is supported by a pre-guideline study in male NMRI mice using only 2 animals/dose and only doses above the current limit dose. The LD50 was determined to be 6.81 mL/kg bw (corresponding to 6200 mg/kg bw) in male mice.

Justification for selection of acute toxicity – dermal endpoint
The reliable GLP compliant OECD Guideline study was chosen. In an OECD 402 and GLP compliant acute dermal toxicity study, the acute dermal LD50 value of the test material in male and female SD rats was found to be greater than 2000 mg/kg bw. No mortalities were observed.

Justification for classification or non-classification

The available data on acute oral and dermal toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.

No data on acute inhalation toxicity is available.