Registration Dossier

Administrative data

Description of key information

Acute toxicity: oral: LD50 > 2500 mg/kg bw (WoE, Target: eq. OECD 401 in rats, non-GLP, rel.2 & Source: OECD 401 in rats, GLP, rel.1)

Acute toxicity: inhalation: waiver

Acute toxicity: dermal: LD50 expected to be > 2500 mg/kg bw (rabbits, non-OECD, non-GLP, rel.4, S + waiver)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Justification for type of information:
REPORTING FORMAT FOR THE ANALOGUE APPROACH
[Further information is included as attachment to the Iuclid section 13]

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across is based on the hypothesis that source and target substances have similar physico-chemical, (eco)toxicological and environmental fate properties because of their structural similarity.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The target and source substances are structurally related, in that both are 1-[(x,x)-dimethyl-1-cyclohexen-1-yl]-pent-4-en-1-one, which can exist as alpha (1-[(5,5)-dimethyl...) or beta (1-[(3,3)-dimethyl...) forms, meaning the position of the double bond in the hexane cycle differs.
The target substance is the isomer alpha (1-(5,5-Dimethyl-1-cyclohexen-1-yl)-4-penten-1-one).
The source substance is a mixture of isomer alpha (1-(5,5-Dimethyl-1-cyclohexen-1-yl)-4-penten-1-one), present as the major constituent between 60 and 75% in the mixture, and corresponding to the target (mono-constituent) substance; and isomer beta (1-(3,3-Dimethyl-1-cyclohexen-1-yl)-4-penten-1-one), present between 25 and 35%.

3. ANALOGUE APPROACH JUSTIFICATION
Based on structural similarity, comparable physicochemical and toxicological properties (incl. acute oral toxicity), the source and the target substances are expected to have similar acute oral toxicity profile.
The study performed on the target substance was neither OECD-compliant nor GLP. Therefore, a weight-of-evidence using also the study performed on the source substance was used to strengthen the acute oral toxicity endpoint. The study design (OECD 401, GLP) is adequate and reliable for the purpose of the prediction based on read-across. The test material used represents the source substance as described in the hypothesis in terms of purity and impurities. The results of the studies are adequate for the purpose of classification and labelling.
Therefore, based on the considerations above, it can be concluded that the results of the acute oral toxicity study conducted in the rat with the source substance are likely to predict the properties of the target substance and are considered as adequate to fulfil the information requirement of Annex VIII, 8.5.1.

4. DATA MATRIX
See Iuclid section13
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across: supporting information
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Only one mortality was observed.
Mortality:
- Nine of ten animals survived the 14 day test. On day 7, male # 9901 was found dead.
Clinical signs:
- On day 1 in am, all animals had decreased locomotion;female #9894 and males #9900 and 9901 appeared dehydrated therefore all animals were given a water bottle. On day 1, at afternoon observations, female #9894 had decreased locomotion, all others appeared normal. There were no other clinical observations noted, all animals appeared normal throughout the 14 day study period.
Body weight:
- All surviving animals had a weight gain by day fourteen of the study period.
Gross pathology:
- There were no gross abnormalities in any of the surviving animals at necropsy.
- Male #9901 was found to have both kidneys dilated, the liver was pale pink, stomach and intestines were distended with gas.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
Based on available data on the source substance, the target substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw and not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).
Executive summary:

In an acute oral toxicity study (limit test), performed according to OECD Guideline No. 401 and in compliance with GLP, a group of Sprague Dawley rats (5/sex) were administered a single oral dose of undiluted test material at 2000 mg/kg bw by gavage. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No clinical signs were observed. One animal was found dead at day 7. All surviving animals showed normal body weight gains after the 14 day study period. No abnormalities were noted at autopsy in the surviving animals. The animal found dead at day 7 has both kidneys dilated, the liver was pale pink, stomach and intestines were distended with gas.

Oral LD50 Combined > 2000 mg/kg bw  

Based on available data on the source substance, the target substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw and is not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From December 15 to 29, 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(age at study initiation and some environmental conditions of animal room not reported)
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
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: Ace Animals, Inc., Boyertown, PA
- Females nulliparous and non-pregnant: yes
- Age at study initiation: not reported
- Weight at study initiation: Males: 1200 - 300 g; females: 200 - 300 g.
- Fasting period before study: the rats were fasted overnight for approximately 18-24 hourss prior to dosing
- Housing: Animals were either single or double housed in suspended stainless steel wire-mesh cages
- Diet: Agway Prolab 2000 rodent feed, ad libitum
- Water: city water, ad libitum
- Acclimation period: at least 7 days prior to the start of testing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature targeted at 21°C
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): not reported
-- Other: during the acclimation and testing perods, each animal was housed and maintained according to The Guide For The Care and Use of Laboratory Animals (NIH 86-23)

IN-LIFE DATES: not reported
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE: not applicable

MAXIMUM DOSE VOLUME APPLIED:
Dose Volume (ml) = [animal weight (kg) x limit dose (2 g/kg)] / Test material density (0.93 g/l)
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: Body weight was recorded in grams for each animal just prior to administration of test substance and weekly thereafter. Body weights were also recorded prior to scheduled sacrifices. All test animals were observed for signs of toxicity and mortality twice daily seven days a week after test material admnistration during two weeks. Observations included the following: circulatory, autonomic and central nervous system, somatomotor activity, behavior patterns, skin and fur, and eyes and mucous membranes.
- Necropsy of survivors performed: Yes; a gross necropsy was performed on all surviving test animals 14 days after dosing. The animals were sacrificed with CO2.
Tissue samples for possible histological examination were taken from each of the ten animals. Tissues taken and preserved in 10% formalin were the lungs, both kidneys and representative sections of the liver.
Statistics:
None
Preliminary study:
Not applicable
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: Only one mortality was observed.
Mortality:
- Nine of ten animals survived the 14 day test. On day 7, male # 9901 was found dead.
Clinical signs:
- On day 1 in am, all animals had decreased locomotion;female #9894 and males #9900 and 9901 appeared dehydrated therefore all animals were given a water bottle. On day 1, at afternoon observations, female #9894 had decreased locomotion, all others appeared normal. There were no other clinical observations noted, all animals appeared normal throughout the 14 day study period.
Body weight:
- All surviving animals had a weight gain by day fourteen of the study period.
Gross pathology:
- There were no gross abnormalities in any of the surviving animals at necropsy.
- Male #9901 was found to have both kidneys dilated, the liver was pale pink, stomach and intestines were distended with gas.
Other findings:
None

None

Interpretation of results:
GHS criteria not met
Conclusions:
Oral LD50 Combined > 2000 mg/kg bw. Not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw and not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).
Executive summary:

In an acute oral toxicity study (limit test), performed according to OECD Guideline No. 401 and in compliance with GLP, a group of Sprague Dawley rats (5/sex) were administered a single oral dose of undiluted test material at 2000 mg/kg bw by gavage. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No clinical signs were observed. One animal was found dead at day 7. All surviving animals showed normal body weight gains after the 14 day study period. No abnormalities were noted at autopsy in the surviving animals. The animal found dead at day 7 has both kidneys dilated, the liver was pale pink, stomach and intestines were distended with gas.

Oral LD50 Combined > 2000 mg/kg bw  

Under the test conditions, the test material is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw and is not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
From August 27 to September 10, 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Reason / purpose for cross-reference:
reference to other study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
(age at study initiation and some environmental conditions of animal room not reported)
Principles of method if other than guideline:
5 g/kg bw of the experimental material was administered into the stomach of ten rats by means of a syringe and dosing needle.
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Remarks:
Sherman-Wistar albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: not reported
- Females (if applicable) nulliparous and non-pregnant: not reported
- Age at study initiation: not reported
- Weight at study initiation: between 200 and 300 g
- Fasting period before study: the rats were deprived of food but not water for 24 hours prior to dosing.
- Housing: not reported
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS: not reported

IN-LIFE DATES: not reported
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE: not applicable

MAXIMUM DOSE VOLUME APPLIED: not specified
Doses:
5000 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: daily for observations; once before dosing and once after the observation period for weighing
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks:
50% test item
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Remarks:
100% test item
Mortality:
None
Clinical signs:
- No untoward symptoms were observed during the first 4-6 hours.
- After 18 hours the animals were slightly depressed, ruffled and dirty. They appeared recovered and normal within 24-36 hours.
Gross pathology:
Gross pathologic examination revealed nothing remarkable.

Table 7.2.1/1 Observations

dosage
Level
g/kg
Number
of Animals
Dosed
Mortalities
Days
Total
Dead
14 days
Total
Survived 14
days
Avg.
Initial Weight
g
Avg.
Final Weight
g
1 2 3 4 5 6 7 8 9 10 11 12 13 14
5.0 5 males 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5 240 275
5.0 5 females 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 5 225 250
Interpretation of results:
GHS criteria not met
Conclusions:
Oral LD50 Combined (100% test item) > 2500 mg/kg bw. Not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw and not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).
Executive summary:

In an acute oral toxicity study (limit test), performed similarly to OECD Guideline No. 401, a group of Sherman-Wistar strain rats (5/sex) were administered a single oral dose of diluted test material (50%) at 5000 mg/kg bw by gavage. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No untoward symptoms were observed during the first 4-6 hours. After 18 hours the animals were slightly depressed, ruffled and dirty. They appeared recovered and normal within 24-36 hours. No abnormalities were noted at autopsy.

Oral LD50 Combined (50% test item) > 5000 mg/kg bw  

Oral LD50 Combined (100% test item) > 2500 mg/kg bw  

Under the test conditions, the test material is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the oral LD50 is higher than 2000 mg/kg bw and not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met).

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 500 mg/kg bw
Quality of whole database:
Weight-of evidence: non-OECD and non GLP-compliant study on the target substance (Klimisch score = 2) + OECD and GLP-compliant study on the source substance (Klimisch score = 1).

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
In accordance with Column 2 of REACH Annex VIII, in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 (acute toxicity by inhalation) and 8.5.3 (acute toxicity by the dermal route) shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. In the present case, inhalation exposure will be lower than dermal exposure because the registered substance has a low vapour pressure (1.34 Pa at 25°C) and a low freezing point (< -20°C), so the potential to generate vapor is low. Nonetheless, considering the use of the substance, exposure to mist can occur. However, based on the absence of acute toxicity by oral route, no mortality is anticipated during the exposure to mist. Hence, dermal exposure is the more likely route of exposure during the manufacture and the use of the substance leading to the penetration of the substance based on its partition coefficient as described below (Log Kow = 4.14 at 25°C).
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
August 27 to September 10, 1979
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Only 3 animals/sex used, diluted substance (50%), Occlusive patch instead of semi-occlusive. The study was not considered sufficient in its own for acute dermal toxicity endpoint and was therefore used in a weight of evidence assessment.
Reason / purpose for cross-reference:
reference to other study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
abraded skin, occlusive dressing and 3 animals/sex used; test material details not given; no details on source, strain, age, housing of animals and environmental conditions of animal room; LD50 calculation method not reported
Principles of method if other than guideline:
Not applicable
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
No data
Species:
rabbit
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 2-3 kg
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
PRETREATMENT
All animals had their backs clipped free of hair 24 h prior to testing. All of the animals had their backs abraded prior to dosing.

TEST SITE
- Area of exposure: Test substance was applied to back of each animal.
- Type of wrap if used: Treated areas were covered with large gauze patches and an impervious material was wrapped snugly around the trunk of each animal.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data, any excess material was removed.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3
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 mortality and clinical signs daily for 14 days. Initial and final bodyweights of animals were recorded.
- Necropsy of survivors performed: Yes; gross necropsies were performed on all animals which died during the 14 day observation period and also on all survivors of the 14 days observation period.
Statistics:
None
Preliminary study:
Not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks:
50% test item
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 000 mg/kg bw
Based on:
test mat.
Remarks:
100% test item
Mortality:
No mortality was observed.
Clinical signs:
No clinical signs were observed.
Body weight:
Surviving animals showed expected gains in bodyweight over the 14-day study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
None

None

Interpretation of results:
study cannot be used for classification
Conclusions:
This study cannot be used for classification since the test substance was not tested up to limit doses which are relevant for classification according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

The study was not considered sufficient in its own for acute dermal toxicity endpoint.
Executive summary:

In an acute dermal toxicity study (limit test) performed similarly to the OECD Guideline No. 402, the abraded skin of albino rabbits (3/sex) was occlusively exposed to diluted test substance (50%) for 24 h at dose of 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination.

No mortality or clinical signs were observed. Surviving animals showed expected gains in bodyweight over the 14-day study period. No abnormalities were noted at necropsy.

Dermal LD50 Combined (50% test item) > 2000 mg/kg bw . Thus, Dermal LD50 Combined (100% test item) > 1000 mg/kg bw

This study cannot be used for classification since the test substance was not tested up to limit doses which are relevant for classification according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

The study was not considered sufficient in its own for acute dermal toxicity endpoint.

Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
In accordance with Column 2 of REACH Annex VIII, testing by dermal route does not need to be conducted because the substance does not meet the criteria for classification for acute toxicity or STOT-SE by the oral route and no systemic toxicity have been observed in in vivo studies with dermal exposure (i.e. in an existing acute dermal toxicity study up to 1000 mg/kg bw conducted on the target substance, and in a GPMT conducted on the source substance at concentration up to 100%) nor in in vivo studies with oral exposure (i.e. in the acute oral toxicity study up to 2500 mg/kg bw).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 500 mg/kg bw
Quality of whole database:
The available study was not conducted according to accepted test guideline and it is of poor quality (Klimisch score = 4). It is not considered sufficient in its own for acute dermal toxicity endpoint but was used together with the acute oral toxicity study (Klimisch score = 1) to conclude on the dermal hazard potential.

Additional information

Acute toxicity: oral

A study on the target substance was identified (Biosearch, 1979, rel.2). This acute oral toxicity study (limit test), was performed before the adoption of the OECD test guidelines and of the GLP, but was conducted similarly to OECD test Guideline No. 401. Rats (5/sex) were administered a single oral dose of diluted test material (50%) at 5000 mg/kg bw by gavage. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. No untoward symptoms were observed during the first 4-6 hours. After 18 hours, the animals were slightly depressed, ruffled and dirty. They appeared recovered and normal within 24-36 hours. No abnormalities were noted at autopsy.

Oral LD50 Combined (50% test item) > 5000 mg/kg bw  

Oral LD50 Combined (100% test item) > 2500 mg/kg bw.

Since this study was neither OECD-compliant nor GLP compliant, it was used within a weigh-of-evidence approach together with a study performed on the source substance (See Iuclid section 13 for read-across justification). The study on the source substance (CLG, 1999, rel.1) was performed according to OECD test Guideline No. 401 and in compliance with GLP. Rats (5/sex) were administered a single oral dose of undiluted test material at 2000 mg/kg bw by gavage. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. No clinical signs were observed. One animal was found dead at day 7. All surviving animals showed normal body weight gains after the 14-day study period. No abnormalities were noted at autopsy in the surviving animals. The animal found dead at day 7 has both kidneys dilated, the liver was pale pink, stomach and intestines were distended with gas.

Oral LD50 Combined > 2000 mg/kg bw  

 

Based on available data on the target and the source substance, the Oral LD50 Combined is > 2500 mg/kg bw.

Acute toxicity: inhalation

In accordance with Column 2 of REACH Annex VIII, in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 (acute toxicity by inhalation) and 8.5.3 (acute toxicity by the dermal route) shall be provided for at least one other route. The choice for the second route will depend on the nature of the substance and the likely route of human exposure. In the present case, inhalation exposure will be lower than dermal exposure because the registered substance has a low vapour pressure (1.34 Pa at 25°C) and a low freezing point (< -20°C), so the potential to generate vapor is low. Nonetheless, considering the use of the substance, exposure to mist can occur. However, based on the absence of acute toxicity by oral route, no mortality is anticipated during the exposure to mist. Hence, dermal exposure is the more likely route of exposure during the manufacture and the use of the substance leading to the penetration of the substance based on its partition coefficient as described below (Log Kow = 4.14 at 25°C).

Acute toxicity: dermal

A study was identified on the target substance (Biosearch, 1979, rel.4). In this acute dermal toxicity study (limit test) performed similarly to the OECD Guideline No. 402, the abraded skin of albino rabbits (3/sex) was occlusively exposed to diluted test substance (50%) for 24 h at dose of 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days and at the end of the study the surviving animals were sacrificed for macroscopic examination. No mortality or clinical signs were observed. Surviving animals showed expected gains in bodyweight over the 14-day study period. No abnormalities were noted at necropsy.

Dermal LD50 Combined (50% test item) > 2000 mg/kg bw .Thus, Dermal LD50 Combined (100% test item) > 1000 mg/kg bw. This study cannot be used alone for classification since the substance was not tested up to limit doses which are relevant for classification according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

However, in accordance with Column 2 of REACH Annex VIII, further study by dermal route does not need to be conducted because the substance does not meet the criteria for classification for acute toxicity or STOT-SE by the oral route and no systemic toxicity have been observed in in vivo studies with dermal exposure (i.e. in an existing acute dermal toxicity study up to 1000 mg/kg bw conducted on the target substance, and in a GPMT conducted on the source substance at concentration up to 100%) nor in in vivo studies with oral exposure (i.e. in the acute oral toxicity study up to 2500 mg/kg bw). Thus, the dermal LD50 is expected to be higher than 2500 mg/kg bw.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity via Oral route:

Based on the available data, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) as the estimated oral LD50 is higher than 2500 mg/kg bw and according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values.

Acute toxicity via Dermal route:

Based on the available data, the substance is not classified according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

Acute toxicity (Inhalation):

No data was available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute oral toxicity study.

Specific target organ toxicity: single exposure (Dermal):

Based on available data via both the oral and dermal route, the classification criteria according to the Annex VI of the Regulation (EC) No 1272/2008 as specific target organ toxicant (STOT) – single dermal exposure Category 1 or 2 are not considered to be met. No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 are not met since narcotic effects were not observed in the acute dermal toxicity study up to 1000 mg/kg bw, nor in the acute oral toxicity study up to 2500 mg/kg bw.

Specific target organ toxicity: single exposure (Inhalation):

No data was available.