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Administrative data

Description of key information

Rats (5/sex/dose) received a single dose of the substance by gavage ( 0.31, 1.0, 1.25, 1.6, 2.5 and  5.0 mL/kg). Mortality (within 4 hours after dosing) was 0, 0, 3, 4 ,9 and 10 at 0.31, 1.0, 1.25, 1.6, 2.5 and  5.0 mL/kg. During the 14 day observation period diarrhea, nausea, sedation and convulsions were observed in surviving animals. Necropsy of decedents was not possible due to orange discoloration of the organs. In survivors no abnormalities were recorded. The LD50 (as assessed by the author of the report) is 1700 mg/kg bw. No correction for purity was made as the composition of the tested substance is similar to that of the substance subject to registration (Bayer 1981)

In an acute dermal toxicity study (limit test) the LD50 of the substance is > 2000 mg/kg bw (Eurofins 2017). No signs of toxicity were observed.

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:
October-November 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann Borchen Germany
- Strain: Wistar TNO/W
- Age at study initiation: males 9 weeks. females 14 weeks
- Weight at study initiation: males 157-185 g, females 151-176 g
- Fasting period before study: yes 16 hours pre-dosing and 4 hours post-dosing
- Housing: 5/sex in Macrolon type III cages
- Diet: Altromin R3 1324 (Altromin GmbH Lage, Germany) ad libitum
- Water: tap water ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1.5 °C
- Humidity (%): 60 °C 5 %
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
0.31, 1.0, 1.25, 1.6, 2.5 and 5.0 mL/kg
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: clinical signs and mortality twice daily
- Body weight: on day 0, 7 and 14
- Necropsy: on all animals
Statistics:
probit analyses
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1.56 mL/kg bw
Based on:
test mat.
95% CL:
>= 1.38 - <= 1.8
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 700 mg/kg bw
Based on:
test mat.
Mortality:
males: 0, 0, 1, 1 ,4 and 5 at 0.31, 1.0, 1.25, 1.6 2.5 and 5.0 mL/kg
females: 0, 0, 2, 3, 5 and 5 at 0.31, 1.0, 1.25, 1.6 2.5 and 5.0 mL/kg
Mortality was within 4 hours after dosing
Clinical signs:
at 1.0 mg/L: nausea in one male and one female
at 1.25 mg/L: diarrhea, nausea and sedation in all animals
at 1.6 and above: diarrhea, nausea, sedation and convulsions in all animals
Body weight:
no data
Gross pathology:
In decedents: orange discoloration prevented examination
in survivors: no findings
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 in rats is 1700 mg/kg bw
Executive summary:

Rats (5/sex/dose) received a single dose of the substance by gavage ( 0.31, 1.0, 1.25, 1.6, 2.5 and  5.0 mL/kg). Mortality (within 4 hours after dosing) was 0, 0, 3, 4 ,9 and 10 at 0.31, 1.0, 1.25, 1.6, 2.5 and  5.0 mL/kg. During the 14 day observation period diarrhea, nausea, sedation and convulsions were observed in surviving animals. Necropsy of decedents was not possible due to orange discoloration of the organs. In survivors no abnormalities were recorded. The LD50 (as assessed by the author of the report) is 1700 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 700 mg/kg bw

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:
experimental study
Adequacy of study:
key study
Study period:
04 September 2017 to 26 September 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Strain: WISTAR rats Crl: WI(Han)
- Females (if applicable) nulliparous and non-pregnant:yes
- Age at study initiation: males 9-10 weeks; females 12-13 weeks
- Weight at study initiation: Males: 235g - 244g; Females 205g - 227g
- Fasting period before study: NA
- Housing: individually in in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding
- Diet: Altromin 1324 maintenance diet for rats and mice ad libitum
- Water: tap water, sulphur acidified to a pH value of approximately 2.8 ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10 %
- Air changes (per hr): 10/hour
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 10% of the body surface
- % coverage: 10% of the body surface
- Type of wrap if used: gauze-dressing and non-irritating tape and was fixed with an additional dressing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with aqua ad injectionem
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 males + 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Clinical signs and irritation (Draize): once within 30 min after dosing, several times upto 4 hours after dosing, daily thereafter
- Body weight: on day 1, 8 and 15
- Necropsy of survivors performed: yes macroscopic examination
Statistics:
NA
Key result
Sex:
male/female
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: irritation was observed
Mortality:
none
Clinical signs:
no systemic effects, red discoloration of the skin in all animals
Body weight:
within normal limits
Gross pathology:
no findings
Other findings:
A crust was observed in 3 of 5 male and 1 of 5 female animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the substance is > 2000 mg/kg bw
Executive summary:

LD50:                                      > 2000 mg/kg bw

Species/strain:                      WISTAR Crl: WI(Han) rats

Vehicle (moistening):             no vehicle used

Number of animals:               5 male and 5 female

Duration of exposure:           24 hours

Method:                                OECD 402, EC 440/2008, Method B.3

Table1:  Results

Sex

Dose
(mg/kg bw)

Number
of Animals

Number
of Intercurrent Deaths

male

2000

5

0

female

2000

5

0

bw = body weight

Signs of systemic toxicity related to dose level used, time of onset and duration:

No treatment-related effects were observed.

Effect on organs (related to dose level):

No treatment-related effects were observed.

Signs of irritation:

No erythema or oedema was observed. A crust was observed in 3 of 5 male and 1 of 5 female animals.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

Based on the available information, the substance needs to be classified as H302: Harmful if swallowed (acute tox cat 4) according to EC Regulation No 1272/2008 (CLP). No classification for acute dermal toxicity is considered necessary.