Palmitoyl chloride

Endpoint summary

Description of key information

The acute LD50 for male and female rats is > 5760 mg/kg (= > 6400 µL/kg) after oral application.

Inhalation of a saturated vapor atmosphere does not represent an acute hazard.

The acute dermal LD50 for female rats ist >1000mg/kg bw <2000 mg/kg bw

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

Dose volumes extending the recommended amounts.

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gassner
- Weight at study initiation: 232 ± 19 g (male), 187 ± 12 (female)

ENVIRONMENTAL CONDITIONS
not reported

Route of administration:

oral: gavage

Vehicle:

other: aqueous emulsion containing Traganth

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2, 20%

MAXIMUM DOSE VOLUME APPLIED: 32 ml/kg = maximum 7.9 ml/animal

Doses:

200, 1600, 3200 and 6400 µL/kg = ca. 180, 1440, 2880, 5760 mg/kg (calculated with a density of 0.9 g/mL)

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Weighing was only at the beginning of the study for dose calculation. Observation of clinical signs was several times on the day of administration and once daily afterwards except on weekends and on holidays.
- Necropsy of survivors performed: yes

Statistics:

Not performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 760 mg/kg bw

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 6.4 mL/kg bw

Mortality:

200 µL/kg: no mortality
1600 µL/kg: no mortality
3200 µL/kg: no mortality
6400 µL/kg: 1/20 animals died within 3 d

Clinical signs:

other: 200 µL/kg: directly after application: squatting posture, depressed respiration; during observation period: piloerection reversible within 1 d 1600 µL/kg: directly after application: abdominal posture, very depressed respiration, semi-closed eye lids, ; p

Gross pathology:

nothing abnormal observed

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

>= 5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

testing of saturated vapour concentration

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(inhalation hazard test as in the annex of the guideline)

Deviations:

no

GLP compliance:

no

Test type:

other: inhalation risk test

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Mean weight at study initiation: males 186 g; females 150 g
no further details given

Route of administration:

inhalation

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

Atmosphere was generated by bubbling 200 l/h dry air (no CO2) through the liquid substance column (volume ca. 50 ml) of about 5 cm above a fritted glass disc in a glass cylinder. The glass cylinder was heated in a water bath. Temperature in the exposure chamber was 20°C. Concentration was stated in the raw data to be 0.37 mg/L (= 32.9 ppm).
The vapour saturation treshold is calculated to be approx. 0.0014 mg/L (at 25°C).

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

8 h

Concentrations:

0.37 mg/L (32.9 ppm) as mean of two trials with 0.363 and 0,375 mg/L, respectively

No. of animals per sex per dose:

6 (3 animals/sex in two trials)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: Weighing was performed at the start and at the end of the study. Observation was several times at the day of exposure and following presumably daily except on weekends and holidays.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

none

Sex:

male/female

Dose descriptor:

LC0

Effect level:

0.37 mg/L air (nominal)

Exp. duration:

8 h

Remarks on result:

other: No mortality observed within 8 h

Mortality:

No mortality observed

Clinical signs:

other: Severe irritations of the mucosa.

Body weight:

Mean body weight after 7 d
males 220 g (+34g); females 171 g (+21 g)
Body weight development was positive

Gross pathology:

Nothing abnormal found

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Dose descriptor:

LD50

Value:

> 1 000 - < 2 000 mg/kg bw

Additional information

oral:

An acute oral toxicity study similar to OECD 401 with acceptable restrictions mostly due to reduced reporting in times before GLP was performed. Groups of 10 rats per sex and dose were administered with 200, 1600, 3200 and 6400 µL/kg of the test substance. The acute LD50 for male and female rats is > 5760 mg/kg (= > 6400 µL/kg) after oral application. Observed clinical signs were squatting or abdominal posture, depressed respiration and apathy. Nothing abnormal was observed at necropsy (BASF, 1970).

Supporting studies for the source substances docosanic acid (CAS 122-85-6).

An acute oral toxicity studay was performed with docosanoic acid (CAS 122-85-6) in accordance to GLP and OECD guideline 401. Five male and five female Sprague-Dawley rats received an oral dose of 2000 mg/kg bw docosanoic acid dissolved in corn oil to a 20% solution via gavage. No effects on general condition and on body weights were found. Also, no abnormality was detected during gross pathology.The oral LD50 value of docosanoic acid was greater than 2000 mg/kg bw (Ohara, 2002).

Acute oral toxicity of docosanoic acid (CAS 122-85-6) was evaluated in a study with Wistar rats which was performed according to GLP and OECD Guideline 401. Five animals of each sex received an oral application of 10 mL/kg bw of docosanoic acid dissolved in DMSO at a dose level of 5000 mg/kg bw by gavage. No clinical signs were noted during the 14-day observation period except ruffled fur and very diminished activity which was seen 20 min after dosing but disappeared within 24 hours. At gross pathology, reddened and swollen mucosa and remnants of the test substance were noted in the stomach. Since no mortality was noted, the LD50 of docosanoic acid was found to be >5000 mg/kg bw (Gloxhuber and Kästner, 1981).

Acute oral toxicity of palmitic acid (CAS 57-10-3) was evaluated in a study performed according to OECD guideline 401, where in a limit test five male and five female Wistar rats received an oral application of 10 mL of 5000 mg/kg bw palmitic acid in DMSO. Clinical signs appeared approximately 20 minutes after dosing including slightly diminished activity and ruffled fur, which completely subsided within 24 hours after dosing. While one female died on day 12 after dosing, all males survived the 14 day observation period. Pathological examination revealed a swelling of the gastric mucosa. Based on the results, the LD50 for palmitic acid was found to be >5000 mg/kg bw (Henkel, 1981).

inhalation:

In a study comparable with the inhalation hazard test described in the Annex of OECD Guideline 403 (adopted 1981) with acceptable restrictions mostly due to reduced reporting in times before GLP rats were exposed for 8 h to a saturated palmitoyl chloride atmosphere. Concentration was stated in the raw data to be 0.37 mg/L(calculated from substance loss). However, vapor saturation threshold is calculated to be approx. 0.0014 mg/L (at 25°C). No mortality and abnormal necropsy findings were reported; observed clinical signs were severe irritation effects on the mucosa. Therefore, inhalation of a saturated vapor atmosphere does not represent an acute hazard (BASF, 1970).

dermal:

Palmitoyl chloride was tested for its toxic effect after application to the skin in the Wistar rat according to the method of OECD 402 (Fixed Dose Procedure). For the study, young adult Wistar rats were dermally exposed to doses of 2000 mg/kg bw and 1000 mg/kg bw of the test item palmitoyl chloride (undiluted or as solution in corn oil Ph.Eur.) to the clipped application site (dorsal and dorso-lateral parts of the trunk and covered by semi-occlusive dressing during the 24-hour exposure period. The application area comprised at least 10% of the total body surface. The animals were observed for 14 days. Mortality or systemic clinical findings were not recorded during the course of the range finding study in the single animal dosed with 2000 mg/kg bw. But due to severe skin findings and resulting distress the animal was humanely killed on day 7 after administration and a second range finding study was carried out. Neither mortality nor systemic clinical findings were recorded during the course of the range finding study in the single animal dosed with 1000 mg/kg bw. Due to the results of the range finding study, a further dose of 1000 mg/kg bw was selected for the stepwise procedure of the main study, with 1 animal per step, to complete the number of two animals. Mortality or systemic clinical findings were not recorded during the course of the main study. No macroscopic pathologic abnormalities were noted in any animal examined at the end of the range finding studies and main study. The LD50 of palmitoyl chloride after dermal application was assessed to be greater than 1000 mg/kg bw and lower than 2000 mg/kg bw in female rats (BASF, 2021).

Justification for classification or non-classification

Based on the available data on acute tocixity the substance is classified as acute dermal cat 4. (H312) according to criteria of Regulation EC/1272/2008 (CLP).