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Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
From September 20, 2011 to October 11, 2011
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
RA study
Justification for type of information:
Refer to the section 13 of IUCLID dataset for details on the read across justification. The acute oral toxicity study with the read across substance is considered sufficient to fulfil the information requirements as further explained in the provided endpoint summary.
Reason / purpose:
read-across source
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
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: At the start of the study the animals were eight to twelve weeks of age
- Weight at study initiation: The bodyweights fell within an interval of ±20% of the mean initial bodyweight of the first treated group
- Fasting period before study: overnight fast
- Housing: The animals were housed in groups of three in suspended solid floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): Free access
- Water (e.g. ad libitum): Free access
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL or 200 mg/mL

- DOSAGE PREPARATION (if unusual): The test substance was freshly prepared, as required, as a suspension at the appropriate concentration in distilled water. The test substance was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using available information on the toxicity of the test substance, 300 mg/kg was chosen as the starting dose.
Doses:
300 mg/kg bw and 2000 mg/kg bw
No. of animals per sex per dose:
3 females at 300 mg/kg bw 6 females at 2000 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for up to fourteen days. Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality
Clinical signs:
Hunched posture and pilo erection were noted in one animal treated at a dose level of 2000 mg/kg. There were no other signs of systemic toxicity.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.

Table 1: Mortality Data

Dose Level mg/kg

Sex

Number of Animals Treated

Deaths During Day of Dosing
(Hours)

Deaths During Period After Dosing
(Days)

Deaths

½

1

2

4

1

2

3

4

5

6

7

8-14

300

Female

3

0

0

0

0

0

0

0

0

0

0

0

0

0/3

2000

Female

3

0

0

0

0

0

0

0

0

0

0

0

0

0/3

Female

3

0

0

0

0

0

0

0

0

0

0

0

0

0/3

Table 2: Individual Clinical Observations - 300 mg/kg bw

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing
(Hours)

Effects Noted During Period After Dosing
(Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

300

1-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-1

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1-2

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0


0 = No signs of systemic toxicity

Table 3: Individual Clinical Observations - 2000 mg/kg bw

Dose Level mg/kg

Animal Number and Sex

Effects Noted After Dosing
(Hours)

Effects Noted During Period After Dosing
(Days)

½

1

2

4

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

2-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-1

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

2-2

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-0

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-1

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

3-2

Female

0

0

0

0

HP

HP

HP

H

0

0

0

0

0

0

0

0

0

0


0 =     No signs of systemic toxicity

H =     Hunched posture

P =     Pilo-erection

Table 4: Individual Bodyweights and Weekly Bodyweight Changes - 300 mg/kg bw

Dose Level

mg/kg

Animal Number
and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

300

1-0 Female

150

165

168

15

3

1-1 Female

156

171

174

15

3

1-2 Female

168

181

183

13

2

Table 5: Individual Bodyweights and Weekly Bodyweight Changes - 2000 mg/kg bw

Dose Level

mg/kg

Animal Number
and Sex

Bodyweight (g) at Day

Bodyweight Gain (g) During Week

0

7

14

1

2

2000

2-0 Female

173

184

196

11

12

2-1 Female

175

189

200

14

11

2-2 Female

160

171

194

11

23

3-0 Female

187

190

195

3

5

3-1 Female

170

177

180

7

3

3-2 Female

175

178

186

3

8

Table 6              Individual Necropsy Findings - 300 mg/kg

Dose Level

mg/kg

Animal Number and Sex

Time of Death

Macroscopic Observations

300

1-0 Female

Killed Day 14

No abnormalities detected

1-1 Female

Killed Day 14

No abnormalities detected

1-2 Female

Killed Day 14

No abnormalities detected

Table 7              Individual Necropsy Findings - 2000 mg/kg

Dose Level

mg/kg

Animal Number and Sex

Time of Death

Macroscopic Observations

2000

2-0 Female

Killed Day 14

No abnormalities detected

2-1 Female

Killed Day 14

No abnormalities detected

2-2 Female

Killed Day 14

No abnormalities detected

3-0 Female

Killed Day 14

No abnormalities detected

3-1 Female

Killed Day 14

No abnormalities detected

3-2 Female

Killed Day 14

No abnormalities detected

Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, the acute LD50 of the substance in rats was determined to be greater than 2000 mg/kg bw.
Executive summary:

A study was conducted to determine the acute oral toxicity of the read across substance, phosphoric acid, mono- and di-C6 -10 -alkyl esters, according to OECD Guideline 423, EU Method B.1 tris and EPA OPPTS 870.1100, in compliance with GLP. A group of three fasted female rats were treated with the test substance at a dose level of 300 mg/kg bw. Based on the results from this dose level a further group of three fasted females were treated at a dose level of 2000 mg/kg bw. Animals were subjected to daily observations and weekly determinations of body weight. Macroscopic examination was performed after terminal sacrifice. The mean body weight gain over the study period was considered to be normal. Finally, no abnormalities were found at macroscopic post mortem examination. Under the study conditions, the acute oral LD50 of the substance in rats was determined to be greater than 2000 mg/kg bw (Sanders, 2012).

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

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral:

A study was conducted to determine the acute oral toxicity of theread across substance, phosphoric acid, mono- and di-C6 -10 -alkyl esters,according to OECD Guideline 423, EU Method B.1 tris and EPA OPPTS 870.1100, in compliance with GLP. A group of three fasted female rats were treated with the test substance at a dose level of 300 mg/kg bw. Based on the results from this dose level a further group of three fasted females were treated at a dose level of 2000 mg/kg bw. Animals were subjected to daily observations and weekly determinations of body weight. Macroscopic examination was performed after terminal sacrifice. The mean body weight gain over the study period was considered to be normal. Finally, no abnormalities were found at macroscopic post mortem examination. Under the study conditions, the acute oral LD50 of the substance in rats was determined to be greater than 2000 mg/kg bw (Sanders, 2012).

Justification for classification or non-classification

Based on an acute oral toxicity study with the read-across substance, phosphoric acid, mono- and di-C6 -10 -alkyl esters, the substance does not warrant classification according to EU CLP (1272/2008) criteria.