Reaction products of ricinoleic acid and linoleic acid and oleic acid with sodium hydroxide and tin (II) chloride

Endpoint summary

Description of key information

The oral LD50 value of ZINN(II)-RICINOLEAT in Wistar rats was established to exceed 2000 mg/kg body weight.
The dermal LD50 value of ZINN(II)-RICINOLEAT in Wistar rats was established to exceed 2000 mg/kg body weight.

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:

2001-06-21 to 2001-07-05

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species : Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC).
Source : Charles River Deutschland, Sulzfeld, Germany.
Number of animals : 6 Animals. Each dose group consisted of 3 animals of one sex (females were nulliparous and non-pregnant).
Age and body weight : Young adult animals (approx. 8 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification : Earmark.
Conditions : A controlled environment was maintained in the room with optimal conditions considered as being approximately 15 air changes per hour, a temperature of 21°C, a relative humidity of 50% and 12 hours artificial fluorescent light and 12 hours dark per day. Deviations from these optimal conditions were noted, but were considered not to have affected study integrity.
Accommodation : Group housing of 3 animals per sex per cage in labelled polycarbonate cages containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Certificates of analysis were examined and then retained in the NOTOX archives. Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet : Free access to standard pelleted laboratory animal diet (from Carfil Quality BVBA, OudTurnhout, Belgium). Certificates of analysis were examined and then retained in the NOTOX archives.
Water : Free access to tap-water. Certificates of quarterly analysis were examined and then retained in the NOTOX archives.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.
Method : Oral gavage, using a stainless steel stomach tube.
Fasting : Food was withheld overnight (for a maximum of 20 hours) prior to dosing until approximately 3-4 hours after administration of the test substance.
Frequency : Single dosage, on day 1.
Dose level (volume) : 2000 mg/kg (1.67 mllkg) body weight. Dose volume calculated as dose level: specific gravity.

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration : 14 days
- Necropsy of survivors performed : yes
- 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. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded: Maximum grade 4: grading slight (1) to very severe (4) Maximum grade 3: grading slight (1) to severe (3) Maximum grade 1: presence is scored (1).
- Necropsy : At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.

Statistics:

The test substance was ranked within LDso value ranges of 0-25, 25-200, 200-2000 or exceeding 2000 mg/kg body weight. No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value). The results were evaluated according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical signs were noted.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

BODY WEIGHTS (GRAM)

Group / Sex	Animal	Day 1	Day 8	Day 15
Group 1 / Females	1	193	228	230
2000 mg/kg	2	175	207	208
	3	198	234	240
	Mean	189	223	226
	ST. DEV.	12	14	16
	N	3	3	3
Group 2 / Males	4	308	374	422
2000 mg/kg	5	294	343	384
	6	292	347	382
	Mean	298	355	396
	ST. DEV.	9	17	23
	N	3	3	3

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

The oral LDso value of ZINN(II)-RICINOLEAT in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

Assessment of acute oral toxicity with ZINN(II)-RICINOLEAT in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in: EC Commission Directive 96/54/EC, Part B.1 tris "Acute Toxicity-Oral, Acute Toxic Class Method" and OECD No.423, "Acute Oral Toxicity - Acute Toxic Class Method". ZINN(II)-RICINOLEAT was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred. No clinical signs were noted. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of ZINN(II)-RICINOLEAT in Wistar rats was established to exceed 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Data from a GLP compliant guideline study with reliability 1.

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:

2000-07-19 to 2000-08-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

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:

Species : Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality). Recognised by international guidelines as the recommended test system (e.g. OECD, EC).
Source : Charles River Deutschland, Sulzfeld, Germany.
Number of animals : 5 males and 5 females (females were nulliparous and nonpregnant).
Age and body weight : Young adult animals (approx. 8 weeks old) were selected. Body weight variation did not exceed +/- 20% of the sex mean.
Identification : Earmark
Conditions : A controlled environment was maintained in the room with optimal conditions considered as being approximately 15 air changes per hour, a temperature of 21°C, a relative humidity of 50% and 12 hours artificial fluorescent light and 12 hours dark per day. Deviations from these optimal conditions were noted, but were considered not to have affected study integrity.
Accommodation : Individually housed in labelled polycarbonate cages containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg, Germany). Certificates of analysis were examined and then retained in the NOTOX archives. Acclimatisation period was at least 5 days before start of treatment under laboratory conditions.
Diet : Free access to standard pelleted laboratory animal diet (from Carfil Quality BVBA, OudTurnhout, Belgium). Certificates of analysis were examined and then retained in the NOTOX archives.
Water : Free access to tap-water. Certificates of quarterly analysis were examined and then retained in the NOTOX archives.

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health. Special attention was paid to the skin to be treated, which was intact and free from any abnormality.
Method : Dermal application.
Clipping : One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
Application : The test substance 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 was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1 D) *, successively covered with aluminium foil and Coban flexible bandage*. A piece of Micropore tape* was additionally used for fixation of the bandages in females only.
*. Manufacturers: Laboratoires Stella s.a., Liege, Belgium (surgical gauze) and 3M, St. Paul, Minnesota, U.S.A. (Coban & Micropore).
Frequency : Single dosage, on day 1.

Duration of exposure:

Application period : 24 hours, after which dressings were removed and the skin cleaned of residual test substance using water.

Doses:

Dose level (volume) : 2000 mg/kg (1.67 ml/kg) body weight. Dose volume calculated as dose level: specific gravity.

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

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. The time of onset, degree and duration were recorded and the symptoms graded according to fixed scales: Maximum grade 4: grading slight (1) to very severe (4) Maximum grade 3: grading slight (1) to severe (3) Maximum grade 1: presence is scored (1).
Necropsy : At the end of the observation period, all animals were sacrificed by asphyxiation using an oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.

Statistics:

No statistical analysis was performed.
The results were evaluated according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC).

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture was noted among the females between days 3 and 8. Chromodacryorrhoea* was noted among the animals on days 1 and 2. * Red secretion from the eye that is spread over the body surface by grooming and commonly noted in albino rats. Erythema, s

Gross pathology:

Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities that were not commonly noted among rats of this age and strain or that were considered toxicologically significant.

Other findings:

Incidental findings:
Pelvic dilatation of the kidneys, found in one female, is commonly noted among rats of this age and strain and was therefore considered not toxicologically significant.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)

Conclusions:

The dermal LD50 value of ZINN(II)-RICINOLEAT in Wistar rats was established to exceed 2000 mg/kg body weight.

Executive summary:

Assessment of acute dermal toxicity with ZINN(II)-RICINOLEAT in the rat.

The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, Part B.3, "Acute Toxicity-Dermal" and OECD No402, "Acute Dermal Toxicity". ZINN(II)-RICINOLEAT was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred. Hunched posture was noted among the females between days 3 and 8. Chromodacryorrhoea was noted among the animals on days 1 and 2. Erythema, scales, fissures and/or scabs were seen in the treated skin-area among the animals during the observation period. The body weight gain during the observation period was within the range expected for rats used in this type of study. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities that were not commonly noted among rats of this age and strain or that were considered toxicologically significant.

The dermal LD50 value of ZINN(II)-RICINOLEAT in Wistar rats was established to exceed 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Data from a GLP compliant guideline study with reliability 1.

Additional information

Acute oral toxicity:

Assessment of acute oral toxicity with ZINN(II)-RICINOLEAT in the rat (Acute Toxic Class Method).

The study was carried out based on the guidelines described in: EC Commission Directive 96/54/EC, Part B.1 tris "Acute Toxicity-Oral, Acute Toxic Class Method" and OECD No.423, "Acute Oral Toxicity - Acute Toxic Class Method". ZINN(II)-RICINOLEAT was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred. No clinical signs were noted. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of ZINN(II)-RICINOLEAT in Wistar rats was established to exceed 2000 mg/kg body weight.

Acute dermal toxicity:

Assessment of acute dermal toxicity with ZINN(II)-RICINOLEAT in the rat.

The study was carried out based on the guidelines described in: EC Commission Directive 92/69/EEC, Part B.3, "Acute Toxicity-Dermal" and OECD No402, "Acute Dermal Toxicity". ZINN(II)-RICINOLEAT was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (day 15). No mortality occurred. Hunched posture was noted among the females between days 3 and 8. Chromodacryorrhoea was noted among the animals on days 1 and 2. Erythema, scales, fissures and/or scabs were seen in the treated skin-area among the animals during the observation period. The body weight gain during the observation period was within the range expected for rats used in this type of study. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities that were not commonly noted among rats of this age and strain or that were considered toxicologically significant.

The dermal LD50 value of ZINN(II)-RICINOLEAT in Wistar rats was established to exceed 2000 mg/kg body weight.

Justification for selection of acute toxicity – oral endpoint
Data from a GLP compliant guideline study with reliability 1.

Justification for selection of acute toxicity – dermal endpoint
Data from a GLP compliant guideline study with reliability 1.

Justification for classification or non-classification

Based on the oral and dermal LD50 values of > 2000 mg/kg bw in rats no classification for acute oral toxicity and acute dermal toxicity is required according to CLP (EU-GHS) Regulation (EC) No 1272/2008 and Directive 67/548/EEC for ZINN(II)-RICINOLEAT.

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