Tricyclodecanedimethanol

Endpoint summary

Description of key information

The oral LD50 (females) of octahydro-4,7-methano-1H-indenedimethanol (TCD-Alcohol DM) was determined to be 2250 mg/kg bw (95% C.I. 2132 - 2374 mg/kg bw) (Hollander/Hoechst AGa, 1975).
The dermal LD50 of octahydro-4,7-methano-1H-indenedimethanol (TCD-Alcohol DM) was determined to be > 10000 mg/kg bw (LD0 = 10000 mg/kg bw; Collier/Safepharm, 1981a).
Inhalational toxicity is not expected due to the low  vapor pressure of octahydro-4,7-methano-1H-indenedimethanol (TCD-Alcohol DM) (data waiving: study not required according to Annex VIII No 8.5.2, column 2).

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions; no data on purity of test substance, limited reporting

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Study is a pre-guideline study, but the method used is similar to OECD Guideline 401 (Acute Oral Toxicity).

GLP compliance:

no

Remarks:

pre-GLP study

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: SPF-Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: own breeding
- Age at study initiation: no data
- Weight at study initiation: 84 - 134 g (mean weigth 100 g)
- Fasting period before study: yes, 16 hrs
- Housing: plastic material cages with planing chips
- Diet (e.g. ad libitum): ALTROMIN 1234 from Altrogge, Lage, Germany
- Water (e.g. ad libitum): tap water
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no date
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:

oral: gavage

Vehicle:

other: Polyglycol 400

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10%
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data

MAXIMUM DOSE VOLUME APPLIED: approx. 5 mL (calculated from concentration, dose, and weight of animals)

Doses:

1600, 2000, 2240, 2500, 4000 mg/kg bw

No. of animals per sex per dose:

10 (only females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weekly recording of body weigth
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

LD50 was determined using probit analysis according to LINDER and WEBER. Confidence limits were calculated according to CAVALLI-SFORZA (Methods of the Department of Applied Mathematics of Hoechst AG).

Sex:

female

Dose descriptor:

LD50

Effect level:

2 250 mg/kg bw

Based on:

test mat.

95% CL:

2 132 - 2 374

Mortality:

1600 mg dose group 0/10 rats
2000 mg dose group 0/10 rats
2240 mg dose group 8/10 rats (7 animals died between 50 and 290 min; 1 animal within 2 days)
2500 mg dose group 7/10 rats (5 animals died within 20 min; 2 animals within 2 days)
4000 mg dose group 10/10 rats (9 animals died within 20 min; 1 animal at 130 min)

Clinical signs:

other: Signs of intoxication: Moribund animals showed disorders of balance, intermittently breathing and died in prone position.

Gross pathology:

No findings during macroscopic examination of surviving and dead animals.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute oral LD50 was 2250 mg/kg bw in female rats. No classifcation required according to EU legislation.

Executive summary:

The acute oral toxicity of octahydro-4,7-methano-1H-indenedimethanol (TCD-Alcohol DM) was determined in groups of 10 fasted, female SPF-Wistar rats receiving a 10% solution of the test material in polyglycol 400 by oral gavage at doses of 1600, 2000, 2240, 2500 and 4000 mg/kg bw. The observation period was 14 days.

The oral LD₅₀ (females) was determined to be 2250 mg/kg bw (95% C.I. 2132 - 2374 mg/kg bw) (Hollander/Hoechst AG, 1975a).

Octahydro-4,7-methano-1H-indenedimethanol is of LOW TOXICITY based on the LD₅₀ in female rats.

This acute toxicity study in the rat ist acceptable. It complies with the retracted OECD guideline 401.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 250 mg/kg bw

Quality of whole database:

The study is a pre-GLP study which is comparable to retracted OECD testing guideline 401 (reliable with restrictions, Klimisch score 2).

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

Study period:

From 11 DEC 1980 to 2 JAN 1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

; occlusive wrapping, individual housing only during exposure

Principles of method if other than guideline:

The study is a pre-guideline study following the method of Noakes and Sanderson (Brit. J. Indust. Med. 1969, 26, 59-64). The method used is similar to OECD Guideline 402 (Acute Dermal Toxicity).

GLP compliance:

no

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: Tuck and Sons Limited, Battlesbridge, Essex, England
- Age at study initiation: no data
- Weight at study initiation: 171 - 237 g
- Fasting period before study: yes
- Housing: individually during the 24 hour exposure period, and then in groups of up to 5 animals; solid floor polypropylene cages furnished with softwood sawdust
- Diet (e.g. ad libitum): rat diet, Nottingham University, Sutton Bonington, Leicestershire, England
- Water (e.g. ad libitum): yes
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 3°C
- Humidity (%): no data
- Air changes (per hr): 20
- Photoperiod (hrs dark / hrs light): 10 /14

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 6 x 10 cm, dorsal and lateral
- % coverage: no data
- Type of wrap if used: aluminium foil thinly covered with test substance hold in place by encircling the trunk of the animal with a strip of elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): sponging with detergent and warm water followed by rinsing with water and drying
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 mL/kg
- Concentration (if solution): pure test substance

Duration of exposure:

24 h

Doses:

10000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation at 0.5, 1 and 4 hours following treatment and then once daily for 14 days, weighing at day 0 and day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD0

Effect level:

10 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: None of the animals died during the 14 days observation period.

Mortality:

None of the treated animals (5 males and 5 females) died.

Clinical signs:

other: All animals exhibited subdued activity up to 4 hours after treatment.

Gross pathology:

No abnormal macroscopic lesions were observed in any of the test animals.

Other findings:

The dermal application caused no irritation and no changes were noted at the terminal examination at 14 days post application.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal toxicity was determined to be > 10000 mg/kg bw. Thus the acute dermal toxicity is very low. No classification is required according to EU legislation.

Executive summary:

In an acute dermal toxicity study, 5 male and 5 female adult Sprague-Dawley rats were dermally exposed to octahydro-4,7 -methano-1H-indenedimethanol (TCD-Alkohol DM) for 24 hours at a single dose of 10000 mg/kg bw.  The exposed area was about 6 x 10 cm. Animals were observed for 14 days.

No mortality was observed.

Thus the dermal LD₅₀ is > 10000 mg/kg bw (LD0 = 10000 mg/kg bw; Collier/Safepharm, 1981a).

Octahydro-4,7 -methano-1H-indenedimethanol (TCD-Alkohol DM) is of low dermal toxicity based on the observed LD₅₀ value.

This acute dermal toxicity study in the rat is acceptable. It complies with the OECD guideline 402

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

10 000 mg/kg bw

Quality of whole database:

The study is a pre-GLP study which is comparable to OECD testing guideline 402 (reliable with restrictions, Klimisch score 2).

Additional information

Acute oral toxicity

The acute oral toxicity of TCD-Alcohol DM was determined in groups of 10 fasted, female SPF-Wistar rats receiving a 10% solution of the test material in polyglycol 400 by oral gavage at doses of 1600, 2000, 2240, 2500 and 4000 mg/kg bw. The observation period was 14 days.

The oral LD50 (females) was determined to be 2250 mg/kg bw (95% C.I. 2132 - 2374 mg/kg bw) (Hollander/Hoechst AG, 1975a).

This acute toxicity study in the rat is acceptable. It complies with the retracted OECD guideline 401.

 

Acute dermal toxicity

In an acute dermal toxicity study, 5 male and 5 female adult Sprague-Dawley rats were dermally exposed to TCD-Alkohol DM for 24 hours at a single dose of 10000 mg/kg bw. The exposed area was about 6 x 10 cm. Animals were observed for 14 days.

No mortality was observed.

Thus the dermal LD50 is > 10000 mg/kg bw (LD0 = 10000 mg/kg bw; Collier/Safepharm, 1981a).

This acute dermal toxicity study in the rat is acceptable. It complies with the OECD guideline 402.

Acute Inhalation toxicity

The vapour pressure of TCD Alcohol DM is calculated to be < 1 hPa. Thus, atmosphere concentrations which can be reached are too low to exert toxic effects. Nelson et. al. (1990) have investigated series of alcohols showing that alcohols with a chain length from C5 on upward do not cause toxic effects due to low atmosphere concentrations achievable (.Journal of the American College of Toxicology 1990 (9): 93-97; Toxicol and Industrial Health 1990 (6): 373-387) (data waiving: study not required according to Annex VIII No. 8.5.2, column 2).

The vapour pressure of alcohols with chain lengths of C6 and longer are known to be too low to cause adverse effects in repeated dose studies (Nelson and coworkers , 1990; supporting study). Therefore, and for animal welfare, no acute inhalation study was conducted.

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

Justification for selection of acute toxicity – inhalation endpoint
Only two routes of exposure required. Inhalation route not relevant for this submission substance of low volatility (low vapour pressure (<1 hPa) and high boiling point).

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

Justification for classification or non-classification

Acute oral toxicity

The acute LD50 in rats was 2250 mg/kg bw. This exceeds clearly the cut-off value for classification according to Regulation (EC) No 1272/2008.

However based on this LD50 value of 2250 mg/kg bw classification into acute oral toxicity category 5 is required according to United nations GHS, 2013 (ST/SG/AC.10/30/Rev.5).

Acute dermal toxicity

The dermal LD50 in rats was > 10000 mg/kg bw. This exceeds clearly the cut-off value for classification according to Regulation (EC) No 1272/2008.

Acute inhalation toxicity

No acute inhalation toxicity test is available. However, inhalational toxicity is not expected due to the low vapor pressure of the submission substance.

Overall, the acute oral, dermal and inhalation toxicity of octahydro-4,7-methano-1H-indenedimethanol (TCD-Alcohol TM) is low and does not require classification.