Registration Dossier

Administrative data

Description of key information

Oral LD50 (OECD 423), rat >=2000 mg/kg bw (limit test)
Dermal LD50 (OECD 402), rat >= 2000 mg/kg bw (limit test)
Acute toxicity by inhalation was not tested according to REGULATION (EC) No 1907/2006, Annex VIII, Section 8.5, Column 2.

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:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(2001)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: WISTAR rats Crl: WI(Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8-9 weeks
- Weight at study initiation: Step 1 (animals 1-3): 159 - 166 g; Step 2 (animals 4-6): 152 - 155 g
- Fasting period before study: Food was withheld from the test animals for 16 to 19 hours prior to the administration.
- Diet (ad libitum): Altromin 1324 maintenance diet for rats and mice (lot no. 0856)
- Water (ad libitum): tap water, sulphur acidified to a pH value of approximately 2.8
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200g/L

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 females per step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A careful clinical examination was made several times on the day of dosing. Thereafter, the animals were observed for clinical signs once daily. The animals were weighed on day 1 (prior to the application) and on days 8 and 15.
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Mortality:
No mortality occured.
Clinical signs:
Clinical signs within the first 3 days after application comprised among others of piloerection, half eyelid-closure, tremor, reduced spontaneous activity, catalepsis and kyphosis. No clinical signs were observed thereafter.
Body weight:
No effects on body weight observed.
Gross pathology:
No findings upon necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
Species:
rat
Strain:
other: WISTAR rats Crl: WI(Han)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 8-9 weeks
- Weight at study initiation: Step 1 (animals 1-3): 159 - 166 g; Step 2 (animals 4-6): 152 - 155 g
- Fasting period before study: Food was withheld from the test animals for 16 to 19 hours prior to the administration.
- Diet (ad libitum): Altromin 1324 maintenance diet for rats and mice (lot no. 0856)
- Water (ad libitum): tap water, sulphur acidified to a pH value of approximately 2.8
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200g/L

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
3 females per step
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A careful clinical examination was made several times on the day of dosing. Thereafter, the animals were observed for clinical signs once daily. The animals were weighed on day 1 (prior to the application) and on days 8 and 15.
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occurred.
Mortality:
No mortality occured.
Clinical signs:
Clinical signs within the first 3 days after application comprised among others of piloerection, half eyelid-closure, tremor, reduced spontaneous activity, catalepsis and kyphosis. No clinical signs were observed thereafter.
Body weight:
No effects on body weight observed.
Gross pathology:
No findings upon necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The whole data base is conclusive and of high quality.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
Acute toxicity by inhalation was not tested according to REGULATION (EC) No 1907/2006, Annex VIII, Section 8.5, Column 2.

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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Bayerisches Landesamt für Gesundheit und Lebensmittelsicherheit
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
other: WISTAR rats Crl: WI(Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: males: 7-8 weeks, females: 11-12 weeks
- Weight at study initiation: males: 221 – 235 g, females: 212 – 229 g.
- Diet (ad libitum): Altromin 1324 maintenance diet for rats and mice (lot no. 0939)
- Water (ad libitum): tap water, sulphur acidified to a pH value of approximately 2.8
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 10%
REMOVAL OF TEST SUBSTANCE
- Washing: The residual test item was removed using aqua ad injectionem
- Time after start of exposure: 24 h
Duration of exposure:
24 h
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: A careful clinical examination was made several times on the day of dosing. Thereafter, the animals were observed for clinical signs once daily. The animals were weighed on day 1 (prior to the application) and on days 8 and 15.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occured.
Mortality:
No mortality occured.
Clinical signs:
No clinical signs of toxicity occurred.
Signs of dermal irritation were observed. Erythema grade 1 was observed on 10/10 animals on day 4 which was fully reversed on day 5 on all animals. Eschar formation was observed from day 4 to day 8 and desquamation was observed beginning on day 6 (10/10 animals both). Desquamation was observed in 7/10 animals until study termination. Scratches were observed in 2 of 5 females.
Body weight:
A decreased body weight was observed for 3/5 females during the first week. However, all females gained weight during the second week. The effects on body weight might be secondary due to the dressing and are considered to be of no toxicological relevance.
The males gained weight throughout the whole study period. For details see table 1 in "Any other information on results incl. tables".
Gross pathology:
Upon gross pathology hernia (liver) into the diaphragm was observed in one female. This incidental finding is not considered to be treatment related.

Table 1: Absolute Body Weights in g and Body Weight Gain in %

Animal No. / Sex

Day 1

Day 8

Day 15

Day 1-15

21 / male

226 g

241 g

282 g

25 %

22 / male

231 g

250 g

292 g

26 %

23 / male

230 g

238 g

274 g

19 %

24 / male

221 g

236 g

270 g

22 %

25 / male

235 g

245 g

282 g

20 %

Mean ± SD

229 ± 5.3 g

242 ± 5.6 g

280 ± 8.5 g

22 ± 3.0 %

26 / female

213 g

215 g

220 g

3 %

27 / female

216 g

213 g

217 g

0 %

28 / female

212 g

205 g

216 g

2 %

29 / female

229 g

227 g

250 g

9 %

30 / female

217 g

223 g

234 g

8 %

Mean ± SD

217 ± 6.8 g

217 ± 8.6 g

227 ± 14.6 g

4 ± 3.9 %

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
Species:
rat
Strain:
other: WISTAR rats Crl: WI(Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: males: 7-8 weeks, females: 11-12 weeks
- Weight at study initiation: males: 221 – 235 g, females: 212 – 229 g.
- Diet (ad libitum): Altromin 1324 maintenance diet for rats and mice (lot no. 0939)
- Water (ad libitum): tap water, sulphur acidified to a pH value of approximately 2.8
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 10%
REMOVAL OF TEST SUBSTANCE
- Washing: The residual test item was removed using aqua ad injectionem
- Time after start of exposure: 24 h
Duration of exposure:
24 h
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: A careful clinical examination was made several times on the day of dosing. Thereafter, the animals were observed for clinical signs once daily. The animals were weighed on day 1 (prior to the application) and on days 8 and 15.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occured.
Mortality:
No mortality occured.
Clinical signs:
No clinical signs of toxicity occurred.
Signs of dermal irritation were observed. Erythema grade 1 was observed on 10/10 animals on day 4 which was fully reversed on day 5 on all animals. Eschar formation was observed from day 4 to day 8 and desquamation was observed beginning on day 6 (10/10 animals both). Desquamation was observed in 7/10 animals until study termination. Scratches were observed in 2 of 5 females.
Body weight:
A decreased body weight was observed for 3/5 females during the first week. However, all females gained weight during the second week. The effects on body weight might be secondary due to the dressing and are considered to be of no toxicological relevance.
The males gained weight throughout the whole study period. For details see table 1 in "Any other information on results incl. tables".
Gross pathology:
Upon gross pathology hernia (liver) into the diaphragm was observed in one female. This incidental finding is not considered to be treatment related.

Table 1: Absolute Body Weights in g and Body Weight Gain in %

Animal No. / Sex

Day 1

Day 8

Day 15

Day 1-15

21 / male

226 g

241 g

282 g

25 %

22 / male

231 g

250 g

292 g

26 %

23 / male

230 g

238 g

274 g

19 %

24 / male

221 g

236 g

270 g

22 %

25 / male

235 g

245 g

282 g

20 %

Mean ± SD

229 ± 5.3 g

242 ± 5.6 g

280 ± 8.5 g

22 ± 3.0 %

26 / female

213 g

215 g

220 g

3 %

27 / female

216 g

213 g

217 g

0 %

28 / female

212 g

205 g

216 g

2 %

29 / female

229 g

227 g

250 g

9 %

30 / female

217 g

223 g

234 g

8 %

Mean ± SD

217 ± 6.8 g

217 ± 8.6 g

227 ± 14.6 g

4 ± 3.9 %

Interpretation of results:
GHS criteria not met
Conclusions:
CLP: not classified
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Isaacs lab stock
- Weight at study initiation: P0304 - male - 2.30 - 2.55 kg, female - 2.83 - 3 kg; P0305 - male - 2.16 - 2.79 kg, female - 2.37 - 2.62 kg
-- Housing: Individually in stainless cages with stainless steel slatted flooring
- Diet: Purina lab rabbit chow, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 7 days minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 to 20.5°C
- Photoperiod (hrs dark / hrs light): 12 hours on/off flurescent lighting

IN-LIFE DATES: From: 1977-12-29 To: 1978-02-13
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Backs of animals (Intact and Abraded skin sites)
- % coverage: Test site covered with 8 ply gauze
- Type of wrap if used: Saran wrap and elastoplast tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test areas were wiped with a wet paper towel
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (2 mL/kg)
- Concentration (if solution): Undiluted
- Constant volume or concentration used: yes
Duration of exposure:
24 h
Doses:
2000 mg/kg bw for each test substance
No. of animals per sex per dose:
3 male and 3 female animals for each test substance (3 animals - intact, 3 animals - abraded)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observation - daily for 14 days post administration; Weighing - Initial and final
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: For both P0304 and P0305 (60% each)
Mortality:
No mortality was observed.
Clinical signs:
P0304 (NH4C12 -13AE3S/ Shell shop) – Erythema was observed on all animals on day 1 and persisted on 3 of 6 for the full 14 days. Edema was observed only on day 3 and only on 2 of 6 animals. Atonia was observed on all animals beginning on day 3. Eschar developed slowly and was questionable on days 3 and 4 but was fully pronounced on day 5 on all animals. Atonia persisted around the eschar area for several days. No atonia was observed on any animal after day 11. The eschar persisted through 14 days on all animals. Desquamation, fissuring and exfoliation were observed on all rabbits.
P0305 (NH4C12 -13AE3S/ Shell CDC) – Erythema was observed on all animals on day 1 and persisted on only 2 rabbits through day 14. Edema was observed on only one rabbit for one day. Eschar and Atonia appeared on all animals by day 3 with eschar formation being questionable on one rabbit only on day 4. The eschar had cleared on this same rabbit by day 14 but persisted on all others through the 14th day. Desquamation was observed on 4 of 6 animals while fissuring and exfoliation were observed on all animals.
Body weight:
Normal body weight gain was observed.
Gross pathology:
Necropsy results for both groups (P0304 and P0305) were not remarkable.
Other findings:
- Organ weights: None
- Histopathology: None
- Potential target organs: None
- Other observations: None
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 for both P0304 (60% active NH4C12 -13AE3S) and P0305 (60% active NH4C12 -13AE3S) is > 2000 mg/kg. Thus, for both test
substances no classification is warranted.
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
According to Guideline.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No effects.
Clinical signs:
No systemic effects.
Body weight:
No effects.
Gross pathology:
No effects.
Interpretation of results:
GHS criteria not met
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Reason / purpose:
read-across source
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
According to Guideline.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No effects.
Clinical signs:
No systemic effects.
Body weight:
No treatment-related effects.
Gross pathology:
No effects.
Other findings:
Moderate to severe dermal irritations at the treatment site were observed following removal of the dressings. 24 h after dermal application of the test substance four male and three female animals showed inflammation of the treated skin. One male and two females showed no skin lesions.
48 h after application an induration of the skin lesions occured and 72 h after application a scab formation was noticed. The scab was fallen off 6 days later in male animals and 12 days later in female animals. On day 14 only one female animal showed residual scabs and a slightly scarred skin.
Interpretation of results:
GHS criteria not met
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Study period:
1977-12-29 to 1978-02-13
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
- 3 males and 3 females were dosed for each test substance instead of 5 males and 5 females
GLP compliance:
no
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: Isaacs lab stock
- Weight at study initiation: P0304 - male - 2.30 - 2.55 kg, female - 2.83 - 3 kg; P0305 - male - 2.16 - 2.79 kg, female - 2.37 - 2.62 kg
-- Housing: Individually in stainless cages with stainless steel slatted flooring
- Diet: Purina lab rabbit chow, ad libitum
- Water: Tap water, ad libitum
- Acclimation period: 7 days minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5 to 20.5°C
- Photoperiod (hrs dark / hrs light): 12 hours on/off flurescent lighting

IN-LIFE DATES: From: 1977-12-29 To: 1978-02-13
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Backs of animals (Intact and Abraded skin sites)
- % coverage: Test site covered with 8 ply gauze
- Type of wrap if used: Saran wrap and elastoplast tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Test areas were wiped with a wet paper towel
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg (2 mL/kg)
- Concentration (if solution): Undiluted
- Constant volume or concentration used: yes
Duration of exposure:
24 h
Doses:
2000 mg/kg bw for each test substance
No. of animals per sex per dose:
3 male and 3 female animals for each test substance (3 animals - intact, 3 animals - abraded)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observation - daily for 14 days post administration; Weighing - Initial and final
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: For both P0304 and P0305 (60% each)
Mortality:
No mortality was observed.
Clinical signs:
P0304 (NH4C12 -13AE3S/ Shell shop) – Erythema was observed on all animals on day 1 and persisted on 3 of 6 for the full 14 days. Edema was observed only on day 3 and only on 2 of 6 animals. Atonia was observed on all animals beginning on day 3. Eschar developed slowly and was questionable on days 3 and 4 but was fully pronounced on day 5 on all animals. Atonia persisted around the eschar area for several days. No atonia was observed on any animal after day 11. The eschar persisted through 14 days on all animals. Desquamation, fissuring and exfoliation were observed on all rabbits.
P0305 (NH4C12 -13AE3S/ Shell CDC) – Erythema was observed on all animals on day 1 and persisted on only 2 rabbits through day 14. Edema was observed on only one rabbit for one day. Eschar and Atonia appeared on all animals by day 3 with eschar formation being questionable on one rabbit only on day 4. The eschar had cleared on this same rabbit by day 14 but persisted on all others through the 14th day. Desquamation was observed on 4 of 6 animals while fissuring and exfoliation were observed on all animals.
Body weight:
Normal body weight gain was observed.
Gross pathology:
Necropsy results for both groups (P0304 and P0305) were not remarkable.
Other findings:
- Organ weights: None
- Histopathology: None
- Potential target organs: None
- Other observations: None
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 for both P0304 (60% active NH4C12 -13AE3S) and P0305 (60% active NH4C12 -13AE3S) is > 2000 mg/kg. Thus, for both test
substances no classification is warranted.
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Occlusive dressing.
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:
According to Guideline.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No effects.
Clinical signs:
No systemic effects.
Body weight:
No effects.
Gross pathology:
No effects.
Interpretation of results:
GHS criteria not met
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Refer to the Category Approach Justification document provided in IUCLID6 Section 13.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
According to Guideline.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No effects.
Clinical signs:
No systemic effects.
Body weight:
No treatment-related effects.
Gross pathology:
No effects.
Other findings:
Moderate to severe dermal irritations at the treatment site were observed following removal of the dressings. 24 h after dermal application of the test substance four male and three female animals showed inflammation of the treated skin. One male and two females showed no skin lesions.
48 h after application an induration of the skin lesions occured and 72 h after application a scab formation was noticed. The scab was fallen off 6 days later in male animals and 12 days later in female animals. On day 14 only one female animal showed residual scabs and a slightly scarred skin.
Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The whole data base is conclusive and of high quality.

Additional information

No data on acute toxicity are available for AES (C8-10, 1-2.5 EO) NH4 (CAS 68891-29-2). Therefore this endpoint is covered by read across to structurally related AES, i.e. AES (C8-10, 1-2.5 EO) Na for oral toxicity and AES (C12-14, 1-2.5 EO) Na (CAS 68891-38-3), AES (C12-14, 1-2.5 EO) TIPA (CAS 174450-50-1), AES (C12 -13, 3 EO) NH4 and AES (C8-10, 1-2.5 EO) Na for the dermal route. The AES reported within the AES category show similar structural, physico-chemical, environmental and toxicological properties. The approach of grouping different AES for the evaluation of their effects on human health and the environment was also made by the Danish EPA (2001) and HERA (2003), supporting the read across approach between structurally related AES.

 

A study addressing acute oral toxicity for the read-across substance AES (C8-10, 1-2.5 EO) Na is available. The study conducted with AES (C8-10, 1-2.5 EO)Na was performed according to OECD Guideline 423 with 6 female Wistar rats in two steps (Z&S, 2012a). Per step 3 animals received 2000 mg/kg bw test substance via oral gavage. The animals were observed daily for clinical signs of toxicity. Body weight was assessed before treatment and on days 8 and 15. Upon study termination animals were sacrificed and gross pathology was performed. No mortality occurred. Clinical signs of toxicity within the first 3 days after application comprised among others of piloerection, half eyelid-closure, tremor, reduced spontaneous activity, catalepsis, and kyphosis. No clinical signs were observed thereafter. No effects on body weight and upon necropsy occurred. The LD50 is greater than 2000 mg/kg bw.

 

Regarding the acute dermal toxicity four studies are available for the read-across substances AES (C12-14; 1-2.5 EO) Na (CAS 68891-38-3), AES (C12-14; 1-2.5 EO) TIPA (CAS 174450-50-1), AES (C12-13, 3 EO) NH4 and AES (C8-10; 1-2.5 EO) Na.

The key study with AES (C8-10; 1-2.5 EO) Na was conducted according to OECD Guideline 402 as a limit test at 2000 mg/kg bw on 5 Wistar rats per sex (Z&S, 2012b). The pure test substance was applied for 24 h under semi occlusive conditions. No mortalities and no clinical signs of toxicity occurred. Hence, the LD50 value is greater than 2000 mg/kg bw. Signs of dermal irritation were observed. Erythema grade 1 was observed on 10/10 animals on day 4 which was fully reversed on day 5 on all animals. Eschar formation was observed from day 4 to day 8 and desquamation was observed beginning on day 6 (10/10 animals both). Desquamation was observed in 7/10 animals until study termination. Scratches were observed in 2 of 5 females. Upon gross pathology hernia (liver) into the diaphragm was observed in one female. This incidental finding is not considered to be treatment related. A further incidental finding was a decreased body weight of 3/5 females after one week. As the females gained weight thereafter and no effect on body weight was observed for males this finding is of no toxicological relevance.

The supporting study conducted with AES (C12-14) Na (CAS 68891-38-3, no data on ethoxylation grade) was performed as limit test conducted according to OECD Guideline 402 with 5 male and 5 female Wistar rats (Clariant, 1989). The test substance (analytical purity 27%) was applied at 2000 mg/kg bw for 24 h under occlusive conditions. No mortalities and no clinical signs of toxicity occurred. Hence, the LD50 value is greater than 2000 mg/kg bw based on the test material and greater than 540 mg/kg bw based on the active ingredient.

The supporting study conducted with AES (C12-14; 2 EO) TIPA (CAS 174450-50-1, analytical purity 83.8%) was performed as limit test conducted according to OECD Guideline 402 with 5 male and 5 female Wistar rats (Sasol, 1997). The test substance was applied at 2000 mg/kg bw for 24 h under semi-occlusive conditions. No mortalities and no clinical signs of toxicity occurred. Findings within this study comprised of local signs of irritation at the application site. Hence, the LD50 value is greater than 2000 mg/kg bw based on the test material.

With AES (C12-13) NH4, a supporting non-GLP study similar to OECD Guideline 402 was carried out on three male and three female New Zealand White rabbits (P&G, 1978a). Both sexes were dosed at 2000 mg/kg bw (analytical purity 60%) under occlusive conditions for 24 h. No mortalities occurred during the conduct of the study. Findings within this study comprised of local signs of irritation at the application site. Based on the above mentioned findings the LD50 is greater than 2000 mg/kg bw based on the test material and greater than 1200 mg/kg bw based on the active ingredient. No mortalities occurred within the above mentioned studies independent of the chain length and the counter ion of the AES. Hence, the LD50 is greater than 2000 mg/kg bw.

 

No studies for acute inhalation toxicity are available. However, testing the potential of acute toxicity via inhalation route of AES (C8-10, 1-2.5 EO) NH4 is considered to be not justified. According to Regulation (EC) No 1907/2006, Annex VIII, Section 8.5, Column 2, in addition to the oral route (8.5.1), for substances other than gases, the information mentioned under 8.5.2 to 8.5.3 shall be provided for at least one other route. As information under 8.5.3 (dermal route) is provided, the requirement is fulfilled by using the most appropriate route of exposure.

AES is mainly used in liquid media and due to its very low vapour pressure [2] inhalation is not viewed as a significant route of exposure. Inhalation of AES may occur by inhalation of aerosols generated by spray cleaners or by inhalation of detergent dusts (e.g. washing powder). Taken into account that the acute toxicity of AES is generally low no further information on acute toxicity is expected by testing for acute inhalation toxicity.

 

References:

Danish EPA - Environmental and Health Assessment of Substances in Household Detergents and Cosmetic Detergent Products (2001). Environmental Project No. 615, pp. 24-28

HERA (2003). Human & Environmental Risk Assessment on ingredients of European household cleaning products Alcohol Ethoxysulphates, Human Health Risk Assessment Draft, 2003. http: //www. heraproject. com.

Justification for classification or non-classification

The available data on acute toxicity do not meet the criteria for classification according to Regulation (EC) No. 1272/2008, and are therefore conclusive but not sufficient for classification.