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Description of key information

The key acute oral toxicity study reports an LD50 value of 4659 mg/kg bw in a reliable study carried out according to the appropriate OECD test guideline and in compliance with GLP (TNO 1986).

The key acute dermal toxicity study reports an LD50 value of >20000 mg/kg bw in a reliable study conducted according to GLP (Cannon Labs, 1979).

In accordance with Column 2 of REACH Annex VIII, the acute toxicity study via the inhalation route (required in Section 8.5.2) does not need to be conducted as reliable data via the oral and dermal routes are available.

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:
6 March - 20 March 1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: young adults
- Weight at study initiation: 100-157 g (males), 112- 156 g (females)
- Fasting period before study: overnight before administration of test material
- Housing: The rats were housed in groups of five, males and females separated, in stainless steel cages with wire screen bottom and front.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-2
- Humidity (%): 40-60
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
maize oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50 g/ 100 ml


MAXIMUM DOSE VOLUME APPLIED: 11.52 ml/kg

Doses:
3335, 4000, 4800, 5760 mg/kg (as a 50% w/v dilution in maize oil)
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: After treatment, the rats were observed frequently for signs of intoxication during the first 4 hours and thereafter at least once daily throughout the observation period. Individual body weights were recorded on day 0, 7 and 14.
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 659 mg/kg bw
95% CL:
> 3 995 - < 5 433
Mortality:
3335 mg/kg dose; deaths 1/5 males, 1/5 females
4000 mg/kg dose; deaths 2/5 males, 1/5 females
4800 mg/kg dose; deaths 1/5 males, 4/5 females
5760 mg/kg dose; deaths 4/5 males; 4/5 females

Deaths occurred between 5 hours and 7 days after dosing.
Clinical signs:
During the first few hours after treatment, none of the rats showed any sign of intoxication. Later on, sluggishness, piloerection and coma were frequently observed.
Body weight:
The individual body weights on day 7 and 14 revealed growth retardation or weight loss in some rats, especially in the first post-treatment week.
Gross pathology:
Macroscopic examination at autopsy of the rats that died after dosing with 9.6 ml/kg and 11.52 ml/kg revealed a food overfilled stomach and empty intestines. The liver and kidneys in these rats showed pale discolouration. Pale discolouration of the kidneys was also found in some rats of these dose groups that survived the observation period. At autopsy of the survivors of the 6.67 and 8 ml/kg dose group, no treatment-related gross alterations were seen, at the end of the observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
An acute oral toxicity LD50 value of >4659 mg/kg bw was reported in a reliable study carried out according to an appropriate OECD Guideline and in compliance with GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
4 659 mg/kg bw

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:
April 10, 1979 - May 2, 1979
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Inc., Pennsylvania
- Housing: Stainless steel, wire mesh cages.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: minimum of 7 days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: ca. 10
- Type of wrap if used: impervious elastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin was wiped clean with a soft cloth and tap water
- Time after start of exposure: 24 hours

Duration of exposure:
24 hours
Doses:
20000 mg/kg
No. of animals per sex per dose:
Two rabbits, 1 male and 1 female were used in the range finding study and six rabbits, 3 male and 3 female were used in the LD50 determination.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Each rabbit was observed 24 hours following dermal application of the test material and daily thereafter. Individual body weights were determined on the day of dosing, day 7 and day 14.
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 20 000 mg/kg bw
Mortality:
Three deaths, two male (day 10 and 13) and one female (day 8), occurred during the study.
Clinical signs:
Twenty-four hours after administration of the test material, all rabbits exhibited erythema with three of the eight rabbits also exhibiting oedema. The irritation on all dose application sites returned to normal by day three and remained so throughout the study. Seven of the eight rabbits exhibited one or more of these clinical signs: diarrhoea, decreased locomotor activity, nasal discharge and salivation.
Body weight:
The weekly mean body weights of both males and females decreased on day seven; increasing on day 14. The mean body weights on day 14, however, were still not as high as the body weights on day 0.
Gross pathology:
Gross necropsies of animals deceased during the study revealed salivation, diarrhoea, injection of the stomach, small intestines, cecum and colon, dark red areas of the lungs, numerous white masses in the liver and numerous white masses throughout the body cavity. The gross necropsies of the rabbits which survived the 14 day study period revealed diarrhoea, nasal discharge, dark red spots on the lungs, numerous small white masses on the liver, colon distended by gas enlargement and discolouring of the gall bladder.
Interpretation of results:
GHS criteria not met
Conclusions:
An LD50 value of >20000 mg/kg bw is reported in a reliable study conducted according to GLP.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
20 000 mg/kg bw

Additional information

The key study for acute oral toxicity reported an LD50 value of 4659 mg/kg bw in a study carried out in accordance with OECD test guideline and GLP (TNO, 1986). Deaths at the different dose levels occurred as follows; 3335 mg/kg, 1/5 males, 1/5 females; 4000 mg/kg dose, 2/5 males, 1/5 females; 4800 mg/kg dose, 1/5 males, 4/5 females. During the first few hours after treatment, none of the rats showed any sign of intoxication. Later on sluggishness, piloerection and coma were frequently observed. The individual body weights on day 7 and 14 revealed growth retardation or weight loss in some rats, especially in the first post-treatment week. Macroscopic examination at autopsy of the rats that died after dosing revealed a food overfilled stomach and empty intestines. It is however considered that the effects seen may have occurred as a result of the condensation reactions in the stomach/gut. The liver and kidneys in these rats showed pale discolouration. Pale discolouration of the kidneys was also found in some rats of these dose groups that survived the observation period. At autopsy of the survivors in the lower dose groups, showed no treatment-related gross alterations, at the end of the observation period.

The key study for acute dermal toxicity reported an LD50 value of >20000 mg/kg bw in rabbit, in a reliable, GLP compliant study (Cannon Labs, 1979). Three deaths occurred during the study; two male (day 10 and 13) and one female (day 8) rabbit. Twenty-four hours after administration of the test material, all rabbits exhibited erythema with three of the eight rabbits also exhibiting oedema. The irritation on all dose application sites returned to normal by day three and remained so throughout the study. Seven of the eight rabbits exhibited one or more of these clinical signs: diarrhoea, decreased locomotor activity, nasal discharge and salivation. The weekly mean body weights of both males and females decreased on day seven; increasing on day 14. The mean body weights on day 14, however, were still not as high as the body weights on day 0. Gross necropsies of animals deceased during the study revealed salivation,

diarrhoea, injection of the stomach, small intestines, cecum and colon, dark red areas of the lungs, numerous white masses in the liver and numerous white masses throughout the body cavity. The gross necropsies of the rabbits which survived the 14 day study period revealed diarrhoea, nasal discharge, dark red spots on the lungs, numerous small white masses on the liver, colon distended by gas enlargement and discolouring of the gall bladder.

The most recent and reliable studies were selected as key.


Justification for classification or non-classification

Based on the available information, no classification is required for 2,4,6-trimethyl-2,4,6-tris(3,3,3-trifluoropropyl)cyclotrisiloxane, in accordance with Regulation (EC) No 1272/2008.