Registration Dossier

Administrative data

Description of key information

No mortality was observed in any reported studies, indicating very low acute toxicity via the oral and dermal exposure routes.

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:
12 - 29 June 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Kisslegg, Germany
- Age at study initiation: Young adult animals (approx. 8-9 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean (first group: 160 - 173 grams; second group: 154 - 169 grams).
- Fasting period before study: Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle.

IN-LIFE DATES: From: 12 - 29 June 2012
Route of administration:
oral: gavage
Details on oral exposure:
GAVAGE METHOD: plastic feeding tubes.

Frequency: single dosage, on Day 1.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 mL/kg) body weight.
Dose volume calculated as dose level (g/kg) / specific gravity.

DOSAGE PREPARATION: The formulations (w/w) were prepared within 2 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test substance.

No. of animals per sex per dose:
6 (2 groups of three females in a stepwise manner)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred
Clinical signs:
Hunched posture was noted in all animals on Day 1.
Body weight:
The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study with female rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, CYASORB® UV-2908 Light Stabilizer does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

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:
08-22 November 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011; including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Wistar strain, Crl:WI (Han)
Sex:
male/female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 11 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean (males: 317 grams; females:207 grams).
- Housing: Individual housing in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
Environmental controls for the animal room were set to maintain 18 to 24°C, a relative humidity of 40 to 70%, approximately 15 room air changes/hour, and a 12-hour light/12-hour dark cycle.

IN-LIFE DATES: From: 08 to 22 November 2012
Type of coverage:
occlusive
Details on dermal exposure:
One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The test substance formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The test substance formulation was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D)*, successively covered with aluminum foil and Coban elastic bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.

Frequency: Single dosage, on Day 1.

Washing: Following application, dressings were removed and the skin cleaned of residual test substance using tap water.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg


No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
VEHICLE Propylene glycol (Merck, Darmstadt, Germany) (specific gravity 1.036)
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

Dose volume: 10 mL/kg

DOSAGE PREPARATION: The formulation (w/w) was prepared within 2 hours prior to dosing using amboured coloured glassware. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test substance.

Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.
Statistics:
None.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Chromodacryorrhoea was noted in two males and two females on Day 1. In addition one female showed piloerection on Day 1.

Scales and/or white staining were seen in the treated skin-area of two males and two females during the observation period. One male showed scales on the left flank during Days 12-13.
Body weight:
The changes noted in body weight gain in males and females were within the range expected for rats used in this type of study and were therefore considered not indicative of toxicity.
Gross pathology:
No toxicological significant abnormalities were found at macroscopic post mortem examination of the animals.

One male showed an enlarged left kidney with watery content and a dilated ureter on the left side.
Based on the incidence this is considered not toxicologically significant.

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.

Based on these results, CYASORB® UV-2908 Light Stabilizer does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the:
- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),
- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Oral:

In an acute oral toxicity study with female rats (NOTOX 2012), performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight. This result was supported by another study on male rat (HRC 1978) that reported an LD50 greater than 5.0 g/kg and nothing remarkable in terms of signs of intoxication, skin irritation, and gross autopsy.

Dermal:

In an acute dermal toxicity study with rats (NOTOX 2012), performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined. This result was supported by a rabbit study (HRC 1978) that reported an LD50 greater than 5.0 g/kg and nothing remarkable in terms of signs of intoxication, skin irritation, and gross autopsy.


Justification for selection of acute toxicity – oral endpoint
No mortality was observed.

Justification for selection of acute toxicity – dermal endpoint
No mortality was observed.

Justification for classification or non-classification

Oral (NOTOX 2012):

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results, CYASORB® UV-2908 Light Stabilizer does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.

Dermal (NOTOX 2012):

In an acute dermal toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.

Based on these results, CYASORB® UV-2908 Light Stabilizer does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the:

- Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2011),

- Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.