Registration Dossier

Oral: The acute oral median lethal dose (LD50) of the test item in the Sherman-Wistar strain rat was found to be greater than 2000 mg/kg bodyweight (LD50 > 16000 mg/kg bw)

Dermal: The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

Inhalation: There will be no exposure to the test material via the inhalation route.

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1980-12-10 to 1980-12-31

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Protocol that complies with scientifically accepted methods, and is sufficiently detailed.

Qualifier:

according to guideline

Guideline:

other: Section 772.112-21 CFR 40.

Deviations:

no

Principles of method if other than guideline:

Five groups of five male albino rats were administered with single dose of 1,000, 2,000, 4,000, 8,000 and 16,000 mg/kg bw and observed for 14 days period during which time the rats were observed for signs of toxicity and mortalities.

GLP compliance:

no

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Sherman-Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Source: No data available.
Age at study initiation: No data available.
Weight at study initiation: average weight between 200~300 g.
Fasting period before study: Feed was withheld overnight prior to dosing.
Housing: No data available.
Diet: ad libitum
Water: ad libitum
Acclimation period: No data available.

ENVIRONMENTAL CONDITIONS
Temperature (°C): No data available.
Humidity (%):No data available.
Air changes: No data available.
Photoperiod: No data available.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

1,000, 2,000, 4,000, 8,000 and 16,000 mg/kg bw

No. of animals per sex per dose:

5/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data available.
- Necropsy of survivors performed: Gross necropsies were performed.

Statistics:

None

Preliminary study:

Not applicable

Sex:

male

Dose descriptor:

LD50

Effect level:

> 16 000 mg/kg bw

Based on:

test mat.

Mortality:

One death occurred after 5-6 h in the 16,000 mg/kg bw dose group and no mortality in the remaining groups.

Clinical signs:

other: - There were no unusual behavioral signs noted at 1000, 2000 and 4000 mg/kg bw. - After 2 h, the animals appeared lethargic and ruffled; they appeared normal within 24 h. - After 1-2 h, the animals were depressed, ruffled and dirty. One death occurred a

Gross pathology:

No gross abnormalities were noted in all animals.

Other findings:

None

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test article when administered to male Sherman-Wistar rats, had an acute oral LD50 of higher than 16,000 mg/kg bw.

Executive summary:

Test Guidance

According to US EPA Section 772.112-21 CFR 40.

Method and material

A single dose of the undiluted test material was administered intragastrically to 5 groups of fasted male albino rats (Sherman-Wistar strain) at each treatment level (1,000, 2,000, 4,000, 8,000, and 16,000 mg/kg bw). The animals were observed for signs of toxicity or behavioral changes during the 14 day observation period. Individual weights were recorded on the day of dosing and at termination.

Results

There were no unusual behavioral signs noted at 1000, 2000 and 4000 mg/kg bw. After 2 h, the animals appeared lethargic and ruffled; they appeared normal within 24 h. After 1-2 h, the animals were depressed, ruffled and dirty. One death occurred after 5-6 h. Within 24 h the condition of the surviving animals had improved. They appeared essentially normal after 48 h. One death occurred after 5-6 h in the 16,000 mg/kg bw dose group and no mortality in the remaining groups. Gross autopsies were performed and nothing remarkable was revealed. The oral LD50 value of test material in rats has been determined to be higher than 16,000mg/kg bw.

Conclusion

In accordance with EU CLP (Regulation (EC) No. 1272/2008), classification is not required.

Endpoint conclusion:

no adverse effect observed

Endpoint conclusion:

no study available

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012-08-08 to 2012-08-22

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 8 to 12 Weeks
- Weight at study initiation: 200 g
- Fasting period before study: None
- Housing: Suspended solid floor polypropylene cages furnished with woodflakes.
- Water: Mains drinking water, ad libitum
- Acclimation period: at least 5 days

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

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Back and flanks
- % coverage: ca. 10% of the total body surface area
- Type of wrap if used: Self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Cotton wool moistened with arachis oil BP to remove any residual test item.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): N/A
- Constant volume or concentration used: yes
- For solids, paste formed: N/A

VEHICLE
- Amount(s) applied (volume or weight with unit):N/A
- Concentration (if solution):N/A
- Lot/batch no. (if required): N/A
- Purity: N/A

Duration of exposure:

24 h

Doses:

Single dose level of 2000 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: Animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Animals were weighed on Days 0, 7 and 14
- Necropsy of survivors performed: Yes, At the end of the study the animals were killed by cervical dislocation.
- Other examinations performed: Clinical signs, body weight, dermal reaction

Statistics:

Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made.

Preliminary study:

Not applicable.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: no mortality was observed.

Mortality:

No mortality was observed.

Clinical signs:

other: There were no signs of systemic toxicity.

Gross pathology:

No abnormalities were noted at necropsy

Other findings:

- Organ weights: No data available
- Histopathology: No data available
- Potential target organs: No data available
- Other observations: No data available

Table1: Individual bodyweights and weekly bodyweight changes

Dose level (mg/kg bw)	Animal no. and sex	Body weight (g) at Day			Body weight (g) during Week
Dose level (mg/kg bw)	Animal no. and sex	0	7	14	1	2
2000	1-0 M	336	343	365	7	22
	1-1 M	318	333	358	15	25
	1-2 M	315	323	335	8	12
	1-3 M	295	311	325	16	14
	1-4 M	336	345	368	9	23
	2-0 F	216	220	214	4	-6
	2-1 F	230	235	236	5	1
	2-2 F	228	229	236	1	7
	2-3 F	224	226	228	2	2
	2-4 F	220	220	226	0	6

Table 2: Dermal irritation observations

Animal Number	Observation	Day
Animal Number	Observation	1	2	3	4	5	6	7	8	9	10	11	12	13	14
Male 1-0	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Male 1-1	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Male 1-2	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Male 1-3	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Male 1-4	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Female 2-0	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Female 2-1	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Female 2-2	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Female 2-3	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Female 2-4	Erythema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Oedema	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	Other	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, the acute dermal LD50 of test item is higher than 2000 mg/kg bw in rats therefore it is not classified according to CLP Regulation (EC) N° (1272-2008).

Executive summary:

Test Guidance

Performed according to OECD Guideline 402

Method and materials

A group of Wistar (RccHan:WIST) rats (5/sex/dose) was given a single dermal application of test item at 2000 mg/kg bw. The test item was placed directly on back and flanks of the skin representing approximately 10 % of the total body surface of the animals. The test site was then covered by a semiocclusive dressing for 24 hours. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and were all sacrificed for macroscopic examination.

Results

No mortality and no clinical signs were observed during the study. There were no signs of dermal irritation. One female showed no gain in bodyweight during the first week but expected gain in bodyweight during the second week. One other female showed expected gain in bodyweight during the first week but bodyweight loss during the second week. Remaining animals showed expected gains in bodyweight over the study period. No macroscopic abnormalities were observed at necropsy. The combined dermal LD50 of test item was considered to be higher than 2000 mg/kg bw in rats.

Conclusion

Under the test conditions, the acute dermal LD50 of test item is higher than 2000 mg/kg bw in rats therefore it is not classified according to CLP Regulation (EC) N° (1272 -2008).

Endpoint conclusion:

no adverse effect observed

Oral

In a key study performed according to US EPA Section 772.112-21 CFR 40asingle dose of the undiluted test material was administered intragastrically to 5 groups of fasted male albino rats (Sherman-Wistar strain) at each treatment level (1,000, 2,000, 4,000, 8,000, and 16,000 mg/kg bw). The animals were observed for signs of toxicity or behavioural changes during the 14 day observation period.

There were no unusual behavioral signs noted at 1000, 2000 and 4000 mg/kg bw. After 2 h, the animals appeared lethargic and ruffled; they appeared normal within 24 h. After 1-2 h, the animals were depressed, ruffled and dirty. One death occurred after 5-6 h. Within 24 h the condition of the surviving animals had improved. They appeared essentially normal after 48 h. One death occurred after 5-6 h in the 16,000 mg/kg bw dose group and no mortality in the remaining groups. Gross autopsies were performed and nothing remarkable was revealed. The oral LD50 value of test material in rats has been determined to be higher than 16,000mg/kg bw.

Dermal

In a key study performed according to OECD Guideline 402 agroup of Wistar rats (5/sex/dose) was given a single dermal application of test item at 2000 mg/kg bw. The test item was placed directly on back and flanks of the skin representing approximately 10 % of the total body surface of the animals. The test site was then covered by a semio-cclusive dressing for 24 hours.

No mortality and no clinical signs were observed during the study. There were no signs of dermal irritation. One female showed no gain in bodyweight during the first week but expected gain in bodyweight during the second week. One other female showed expected gain in bodyweight during the first week but bodyweight loss during the second week. Remaining animals showed expected gains in bodyweight over the study period. No macroscopic abnormalities were observed at necropsy. The combined dermal LD50 of test item was considered to be higher than 2000 mg/kg bw in rats.

Inhalation

According to REACH Annex XIII Section 8.5 information on acute toxicity will be provided for at least one other route in addition to the oral route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. The substance is a waxy hydrophobic solid with a vapour pressure of 0.009 Pa at 25 °C and is used in lubricants by workers and consumers. It is expected that inhalation exposure from these uses will be low and that the most likely route of exposure for workers and consumers is the dermal route. Testing for acute toxicity via the inhalation route is, therefore, not required.

Under the test conditions, the acute oral and dermal LD50 of test item are higher than 2000 mg/kg bw in rats therefore it is not classified according to CLP Regulation (EC) No. 1272/2008.