Pidolic acid

Endpoint summary

Description of key information

A study was performed to assess the acute oral toxicity of the substance in the Wistar strain rat at a dose of 2000 mg/kg bw. There were no deaths. There were no signs of systemic toxicity. All animals showed expected gains in body weight. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the substance in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bw.

A study was performed to assess the acute inhalation toxicity of the test item in the Wistar strain rat. A troup of ten rates (five males and five females) were exposed to a dust atmosphere (5mg/L) of the test item for 4 hours using a nose only exposure system, followed by a 14 or 35 days observation period. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths. The acute inhalation median lethal concentration (LC50) of the test item in the Wistar strain rat was estimated to be greater than 5.00 mg/L.

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:

14 December 2016 - 17 January 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Specific details on test material used for the study:

Batch number: 20140124
Physical state/Appearance: white crystalline solid
Storage Conditions: room temperature in the dark

Species:

rat

Strain:

Wistar

Remarks:

RccHan™:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

The females were nulliparous and non-pregnant. After an acclimatization period of at least 5 days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals were 8 to 12 weeks of age. With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to mains drinking water and food. The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The volume administered to each animal was calculated according to the fasted body weight at the time of dosing.

Doses:

2000 mg/kg bw.

No. of animals per sex per dose:

Five.

Control animals:

no

Details on study design:

A single animal was treated with 2000 mg/kg bw dose. In the absence of toxicity at a dose level of 2000 mg/kg, an additional four animals were treated with the same dose.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bw.

Executive summary:

A study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat. Following a sighting test at a dose level of 2000 mg/kg bw, an additional four fasted female animals were given a single oral dose of the substance, as a solution in distilled water, at a dose level of 2000 mg/kg bw. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths. There were no signs of systemic toxicity. All animals showed expected gains in body weight. No abnormalities were noted at necropsy. The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Sufficient to address requirements.

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

Study period:

09 January 2017 to 22 February 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

2009

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

1998

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source (i.e. manufacturer or supplier) and lot/batch number of test material:
- Batch Number: 20140124
- Purity: 99.92%

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: white crystalline solid, room temperature in the dark.

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing (e.g. warming, grinding): In order to facilitate aerosolisation and reduce particle size, the test item was ground using a Retsch Planetary Ball Mill (Retsch (UK) Ltd, UK) prior to use. The absorption of the test item was not determined.

FORM AS APPLIED IN THE TEST (if different from that of starting material)
- Specify the relevant form characteristics if different from those in the starting material, such as state of aggregation, shape of particles or particle size distribution: Aerosol

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: male and female RccHan : WIST strain rats were supplied by Envigo RMS (UK) Limited Oxon, UK.
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 12 weeks old
- Weight at study initiation: 200 - 350 g
- Housing: The animals were housed in groups of up to five by sex in solid-floor polypropylene cages with stainless steel lids, furnished with softwood flakes.
- Diet (e.g. ad libitum): With the exception tot he exposure period, free access to mains drinking water and food was allowed throughout the study.
- Water (e.g. ad libitum): With the exception tot he exposure period, free access to mains drinking water and food was allowed throughout the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- The temperature and relative humidity were set to achieve limits of 19 to 25 degrees and 30 - 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours continuous dark. The animals were retained in this accommodation at all times except during the exposure period.

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

3.65 µm

Geometric standard deviation (GSD):

3.06

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A dust atmosphere was produced from the test item using a SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany) located adjacent to the exposure chamber. The SAG 410 was connected to a metered compressed air supply.
- Exposure chamber volume: The cylindrical exposure chamber has a volume of approximately 30 liters.
- Method of holding animals in test chamber: individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber O ring.
- Source and rate of air (airflow): Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the SAG 410.
- Method of conditioning air: Compressed air was supplied by means of an oil free compressor and passed through a water trap and respiratory quality filters before it was introduced to the SAG 410.
- System of generating particulates/aerosols: A dust atmosphere was produced from the test item using a SAG 410 Solid Aerosol Generator (TOPAS GmbH, Dresden, Germany) located adjacent to the exposure chamber.
- Method of particle size determination: The particle size of the generated atmosphere inside the exposure chamber was determined three times during the exposure period using a Marple Personal Cascade Impactor (Wetech IS Ltd, Beds., UK).
- Treatment of exhaust air: the extract from the exposure chamber passed through a scrubber tap and was connected with a high efficiency filter to a metered exhaust system. The chamber was maintained under negative pressure.
- Temperature, humidity, pressure in air chamber: The temperature and relative humidity inside the exposure chamber were measured by an electronic thermometer/humidity meter located in a vacant port in the animals breathing zone of the chamber and recorded every 30 minutes throughout the 4-hour exposure period.

TEST ATMOSPHERE
- Brief description of analytical method and equipment used: The actual chamber concentration was measured at regular intervals during each exposure period. The gravimetric method used glass fiber filters placed in a filter holder.
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: the proportion percentage of aerosol less than 10.4, 7.7, 4.1, 1.3, 0.9 and 0.56 um um was calculated.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): MMAD was determined (as the 50% point). GSD was calculated.

Analytical verification of test atmosphere concentrations:

no

Duration of exposure:

4 h

Concentrations:

5.00 mg/L

No. of animals per sex per dose:

10 (5 males, 5 females)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days or 35 days
- Frequency of observations and weighing: at hourly intervals during exposure, 1 hour after termination of exposure and subsequently once daily for 14 or 35 days
- Necropsy of survivors performed: yes
- Clinical signs including body weight: Individual body weights were recorded on arrival, prior to treatment on the day of exposure and on days 1, 3, 7 and 14 (all animals) and days 28 and 35 (males only)
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: all animals were observed for clinical signs at hourly intervals during exposure immediately on removal from the restraining tubes at the end of exposure, 1 hour after termination of exposure and subsequently once daily for 14 or 35 days. During necropsy, the respiratory tract was subjected to a detailed macroscopic examination for signs of irritancy or local toxicity.

Key result

Sex:

female

Dose descriptor:

LC50

Effect level:

> 5 mg/L air (nominal)

Based on:

test mat. (dissolved fraction)

Exp. duration:

4 h

Key result

Sex:

male

Dose descriptor:

LC50

Effect level:

> 5 mg/L air (nominal)

Based on:

test mat. (dissolved fraction)

Exp. duration:

4 h

Mortality:

None. All animals survived until termination

Clinical signs:

irregular respiration

Remarks:

decreased respiration, noisy respiration

Body weight:

- other body weight observations:
all males and two females showed body weigh loss 1 day after dosing. Incidents of body weight loss or no gain in body weight were noted between days 1 to 14. One male showed no gain in bod weight from Day 28 to 35.

Gross pathology:

Dark patches on the lungs were noted at necropsy of one female. No macroscopic abnormalities were noted at necropsy of the remaining animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute inhalation median lethal concentration (LC50) of the test item in the Wistar strain rat was estimated to be greater than 5.00 mg/L.

Executive summary:

A study was performed to assess the acute inhalation toxicity of the test item in the Wistar strain rat. A troup of ten rates (five males and five females) were exposed to a dust atmosphere (5mg/L) of the test item for 4 hours using a nose only exposure system, followed by a 14 or 35 days observation period. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths. The acute inhalation median lethal concentration (LC50) of the test item in the Wistar strain rat was estimated to be greater than 5.00 mg/L.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

> 5 mg/L air

Physical form:

inhalation: dust

Quality of whole database:

Sufficient to address requirements.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure (e.g. skin irritation, skin sensitisation)

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Sufficient to address requirements

Justification for classification or non-classification

Based on the findings of a reliable acute oral toxicity study conducted on the substance, classification of the substance is not justified.

Based on the findings of a reliable acute inhalation toxicity study conducted on the substance, classification of the substance is not justified.