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Administrative data

Description of key information

Based on read-across from Alcohols, lanolin (CAS No. 8027-33-6):
Oral: LD50 (rat, m/f) > 2000 mg/kg bw (OECD 401, GLP)
Dermal: LD50 (rat, m/f) > 2000 mg/kg bw (OECD 402, GLP)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance Alcohols, lanolin (CAS No. 8027-33-6). In accordance to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Dose volume of 20 mL/kg bw used to administer dosage of 2000 mg/kg bw. Dose volume should not normally exceed 10 mL/kg for aqueous vehicles. Does not affect relevance of results produced.
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
yes
Remarks:
Dose volume of 20 mL/kg bw used to administer dosage of 2000 mg/kg bw. Dose volume should not normally exceed 10 mL/kg for aqueous vehicles. Does not affect relevance of results produced.
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of inspection: May and June 2000. Date of signature: 2nd August 2000
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 Deutschland GmbH, Sandhofer Weg 7, D-97633, Sulzfeld
- Age at study initiation: Males - 36 days, Females - 45 days
- Weight at study initiation: 164 to 210 g
- Fasting period before study: 16 hours
- Housing: Granulated textured wood was used as bedding material for the cages. During the 14-day observation period animals were kept in groups of 2 or 3 animals in MARKOLON cages (type III).
- Diet: ad libitum
- Water: tap water, as libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 50 ± 15
- Photoperiod (hrs dark / hrs light): 12 /12
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 100 mg/mL
- Amount of vehicle (if gavage): 20 mL/kg bw

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg
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: Observations were performed before and immediately, 5, 15, 30 and 60 minutes, as well as 3, 6 and 24 hours after administration. All surviving animals were observed daily for a period of 14 days.
- Necropsy of survivors performed: yes. Gross pathological changes were recorded.
- Other examinations performed: during the follow-up period, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and smotomotor activity, behavious pattern. Attention paid to possible tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Statistics:
Standard deviation
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality observed.
Clinical signs:
No substance-related findings.
Body weight:
No inhibition of bodyweight gain.
Gross pathology:
No substance-related findings.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance is not classified as toxic or harmful by the oral route of exposure.
CLP: not classified
DSD: not classified
Executive summary:

A study was conducted to determine the oral toxicity of the test substance following the OECD Guidelne 401 and EU Method B.1.

Under the test conditions (a single oral dose of the test material at 2000 mg/kg bw) to rats revealed no toxic symptoms.

The substance is not classified as toxic or harmful by the oral route of exposure.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2 due to read-across) and consistent studies from a reference substance with similar structure and intrinsic properties. Read-across is justified mainly based on common origin, the target substance being a distillation fraction of the source substance (refer to endpoint discussion for further details).
The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, in accordance with Annex XI, 1.5, 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:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
23 March 2010 - 06 April 2010
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance Alcohols, lanolin (CAS No. 8027-33-6). In accordance to the ECHA guidance document "Practical guide 6: How to report read-across and categories (March 2010)", the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.
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
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of Inspection: 15 Septemeber 2009 Date of Signature: 26 November 2009
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:
Animals: Rat, HsdRccHan: WIST

Rationale: Recognized by international guidelines as a recommended test system.

Breeder: Harlan Laboratories UK Limited, Bicester, Oxon, UK.

Number of Animals per Group: 5 males and 5 females

Total number of Animals: 5 males and 5 females

Age when treated: At the start of the study the animals weighed at least 200 g, and were eight to twelve weeks of age. The weight variation did not exceed ± 20% of the mean weight for each sex.

Identification: After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card.

Acclimatization: At least 5 days under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

Environmental Conditions:
Conditions:
The temperature and relative humidity were within the range of 19 to 25 °C and 30 to 70 % respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Accommodation:
The animals were housed in suspended solid-floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study.

Diet:
Free access food (2014 Teklad Global Rodent diet supplied by Harlan Teklad, Blackthorn, Bicester, Oxon, UK) was allowed throughout the study. The diet was routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

Water:
Free access to mains drinking water was allowed throughout the study. The drinking
water was routinely analysed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
Type of coverage:
semiocclusive
Vehicle:
arachis oil
Details on dermal exposure:
One day before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10 % of the total body surface.

Using available information on the toxicity of the test material, a single group of animals was treated as follows:

Dose Level Number of Rats
(mg/kg) Male Female
2000 5 5

The animals were caged individually for the 24 hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self adhesive bandage. The animals were caged individually for the 24 hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and
scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the
Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value

No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth) 4

Oedema Formation

No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well-defined by definite raising) 2
Moderate oedema (raised approximately 1 millimetre) 3
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) 4

Any other skin reactions, if present were also recorded.

Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.

At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external
examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were
retained.

Rationale: The dermal route was selected as the most appropriate route of exposure and the results of the study are believed to be of value in predicting the likely toxicity of the test material to man.
Statistics:
No statistical analysis was performed.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical signs were observed during the course of the study.

There were no signs of dermal irritation. Erythema and edema scores were all 0 at all reading time points (1-14 days post-exposure).
Body weight:
Animals showed expected gains in bodyweight over the study period except for one female which showed no gain in bodyweight during the first week with expected gain in bodyweight during the second week.
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 dermal median lethal dose (LD50) of the test material in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.
CLP: not classified
DSD: not classified
Executive summary:

IntroductionThe study was performed to assess the acute dermal toxicity of the test material in the Wistar strain rat. The method was designed to meet the requirements of the following:

§        OECD Guidelines for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987)

§        Method B3 Acute Toxicity (Dermal) of CommissionRegulation (EC) No. 440/2008

Method. A group of ten animals (five males and five females) was given a single, 24‑hour, semi‑occluded dermal application of the test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality. There were no deaths.

Clinical Observations. There were no signs of systemic toxicity.

Dermal Irritation. There were no signs of dermal irritation.

Bodyweight. Animals showed expected gains in bodyweight over the study period except for one female which showed no gain in bodyweight during the first week with expected gain in bodyweight during the second week.

Necropsy. No abnormalities were noted at necropsy.

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 2 due to read-across) from a reference substance with similar structure and intrinsic properties. Read-across is justified mainly based on common origin, the target substance being a distillation fraction of the source substance (refer to endpoint discussion for further details).
The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI,1.5, of Regulation (EC) No 1907/2006.

Additional information

Justification for grouping of substances and read-across

There are no acute toxicity studies available for Alcohols, lanolin, distn. residues (CAS No. 90622-40-5). In order to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from an analogue substance is conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby physicochemical, toxicological and ecotoxicological properties may be predicted from data for reference substance(s) by interpolation to other substances on the basis of structural similarity, the substance Alcohols, lanolin (CAS No. 8027-33-6) is selected as reference substance for assessment of acute toxicity.

The read-across is mainly based on the common origin of the source and target substances, as the target substance is generated from the source substance by distillation, the target substance being the high-boiling fraction (residue) of the distillation process. A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

Acute toxicity: oral

The acute toxicity of Alcohols, lanolin by the oral route has been investigated in rats in a GLP-compliant study conducted according to OECD guideline 401 (Leuschner, 2001). Groups of 5 animals per sex were given test item diluted in sesame oil in a single dose of 2000 mg/kg bw by gavage. No mortality occurred and no clinical signs of toxicity were observed up to the end of the 14-day observation period. Likewise, no inhibition of body weight gain was noted. Gross pathological examination revealed no substance-related findings. The oral LD50 in male and female rats was estimated to be > 2000 mg/kg bw.

In an earlier study performed following a method similar to OECD guideline 401 and under GLP conditions, groups of 5 male and 5 female rats were given a single oral dose of the test material (diluted in mineral oil) at 5000 mg/kg bw. Two animals died during the 14-day observation period. The LD50 was therefore estimated to be > 5000 mg/kg bw.

Overall, the available data indicate that the substance Alcohols, lanolin is not harmful following acute oral exposure.

Acute toxicity: inhalation

This information is not available.

In accordance with Column 2 of Annex VIII, Section 8.5, of Regulation (EC) No 1907/2006, testing by the inhalation route is not appropriate since human exposure to vapours, aerosols, particles or droplets of inhalable size is unlikely taking into account the nature and use(s) of the substance.

Acute toxicity: dermal

The acute toxicity of Alcohols, lanolin by the dermal route has been investigated in rats in a GLP-compliant study conducted according to OECD guideline 402 (Bradshaw, 2010). Five male and five female rats were dermally exposed to the test item (diluted in arachis oil) at 2000 mg/kg bw for 24 h under semiocclusive conditions. There were no deaths during the study. No clinical signs of toxicity were observed up to the end of the 14-day observation period. Body weight gain was not affected, except for one female which showed no body weight gain in the first week post-exposure, but expected body weight gain in the second week. No abnormalities were noted at necropsy. Furthermore, there were no signs of skin irritation; erythema and edema scores were all 0 in all 10 animals at all reading time points (1-14 days post-exposure). The dermal LD50 in male and female rats was estimated to be > 2000 mg/kg bw.

In conclusion, the available data show that the substance Alcohols, lanolin is not acutely toxic by the dermal route.

Conclusions for acute toxicity

There are no acute toxicity studies available for Alcohols, lanolin, distn. residues. In order to fulfil the standard information requirements of Annex VIII, Section 8.5, of Regulation (EC) No 1907/2006, hazard assessment is conducted by means of read-across from the source substance Alcohols, lanolin in accordance with Annex XI, Section 1.5.

The substance Alcohols, lanolin has been tested for acute oral and dermal toxicity in adequate and reliable studies. In male and female rats exposed to the substance at the limit dose level of 2000 mg/kg bw by the oral and dermal routes, respectively, no mortality occurred and no toxicologically relevant systemic effects were observed. After dermal application, there were no indications for skin irritation. The oral and dermal LD50 values are both > 2000 mg/kg bw.

Based on the read-across approach, the substance Alcohols, lanolin, distn. residues is considered to be not toxic after acute oral and dermal exposure.

Information on the acute toxicity by inhalation is not available. Testing by the inhalation route is not appropriate based on the nature of the substance and unlikeliness of human exposure under normal conditions of use.


Justification for selection of acute toxicity – oral endpoint
Hazard assessment is conducted by means of read-across from a structural analogue/surrogate. The selected study is the most adequate and reliable study based on the identified similarities in structure/composition and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for selection of acute toxicity – dermal endpoint
Hazard assessment is conducted by means of read-across from a structural analogue/surrogate. The selected study is the most adequate and reliable study based on the identified similarities in structure/composition and intrinsic properties between source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Justification for classification or non-classification

Based on read-across from the source substance Alcohols, lanolin (CAS No. 8027-33-6) following an analogue approach, the available data on the acute toxicity of Alcohols, lanolin, distn. residues do not meet the classification criteria according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

Data are lacking for acute toxicity by inhalation.