Registration Dossier

Administrative data

Description of key information

There is no acute oral and dermal toxicity study because of the corrosivity properties of heptanoic acid.

There is one acute toxicity Inhalation study (Cascieri, 1990): LC50 > 4.6 mg/l for female and male rats (equivalent to OECD Guideline 403)

Key value for chemical safety assessment

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:
From 14 November 1990 To 28 November 1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 1b Comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc. Kingston, New York 12484
- Age at study initiation: males 7 weeks and females 8 weeks (approximatively)
- Weight at study initiation: Males 228 g (220-233) and females 197 g (190-202)
- Fasting period before study:
- Housing: individually housed after one week of acclimatation period
- Diet : ad libitum, standard pellet laboratory diet (Purina Rodent Laboratory Chow Brand Animal Diet #5001)
- Water : ad libitum, automated watering system
- Acclimation period: one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-24
- Humidity (%): 40-70
- Air changes (per hr): no data
- Photoperiod : 12 hrs dark / 12 hrs light


IN-LIFE DATES: From: 7 November 1989 To: 28 November 1989
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglas whole-body exposure chamber with a glass front
- Exposure chamber volume: 100 liters
- Method of holding animals in test chamber: not restrained
- Source and rate of air: The exposure chamber was operated dynamically at a calibrated airflow rate of 20.0 liters per minute. This flow rate was calculated to provide one complete air change every 5.0 minutes and a 99 % equilibrium time of 23 minutes.
- Method of conditioning air:
- System of generating particulates/aerosols: appropriate amounts of n-heptanoic acid were placed into a 500 milliliters (ml) Erlenmeyer flask and connected to an FMI fluid metering pump, model RP-G-6 with a 1/4 piston and an initial pump setting of 20 %. The test substance was fed through 1/8 teflon tubing from the pump directly into the liquid inlet of an air atomizing nozzle. House-supply air was delivered to a union carbide regulator and a USG backpressure gauge (at a constant backpressure of 26 pounds per square inch, psi) into the air inlet of the atomizer to generate the aerosol. The test atmosphere was directed into the inlet portal of the exposure chamber which housed the animals.
- Method of particle size determination: Samples for particle size distribution assessment were drawn once per hour using a cascade impactor. The mass median aerodynamic diameter, geometric standard deviation and percent of particles <= 1 and <= 10 microns were calculated based on the amount of material collected on the impactor stages using a graphical analysis of an assumed lognormal distribution.
- Treatment of exhaust air: no data
- Temperature, humidity, pressure in air chamber: A Taylor wall thermometer was used to continuously monitor air temperature, an Airguide humidity indicator was used to continuously monitor relative humidity, a Dwyer flowmeter was used to continuously monitor static pressure within the exposure chamber. Recordings of temperature, relative humidity and airflow rate were made every half-hour during exposure.


TEST ATMOSPHERE
- Brief description of analytical method used: Sample for gravimetric determination of n-heptanoic acid exposure level were drawn from the exposure chamber using Whatman glass microfibre filter paper mounted open-faced in a Gelman filter holder. Samples were withdrawn once per hour from the normal sampling portal and once during exposure from the distribution sampling portal. The filter papers were weighed before and after sample collection, and the gravimetric concentration in mg/l was calculated by dividing theweight difference in milligrams by the volume of air sampled in liters.
- Samples taken from breathing zone: yes





Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
4.6 mg/l (measured)
28 mg/l (nominal concentration)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Observations: Day of exposure: All animals were observed individually, immediately prior to exposure, as a group at approximately fifteen-minute intervals during the first hour of exposure and hourly for the remainder of the exposure period. All animals were observed individually upon removal from the chamber (half-hour after exposure was completed) and hourly for two hours post-exposure. Detailed physical observations were recorded at each interval. Post-exposure: Detailed observations were recorded for survivors once daily; viability was assessed twice daily.
Body weight: Days 1 (immediately prior to exposure), 2, 3, 5, 8 and 15 (just prior to sacrifice)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
No statistics were performed.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 4.6 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
Four rats (two male and two female animals) were found dead upon removal of the animals from the chamber. All other animals survived the duration of the study.
Clinical signs:
other: Observations noted during exposure included labored breathing, gasping, lacrimation, nasal discharge, matted coat and eye closure. Signs exhibited by surviving animals upon removal from the chamber and during the two hour post-exposure observation period
Body weight:
Significant weight losses were observed for a few days following exposure. Recovery of weight occurred over time and all surviving animals were in excess of their pre-exposure body weight by termination of the study.
Gross pathology:
Reddening of the lungs and various other tissues were observed in the animals found dead. This was not considered uncommon for animals which died and were not exsanguinated prior to postmotem examination. The coat in three animals was wet and matted. This was considered to be due to deposition of the test article on the animals and not considered to be of toxicologic significance. Opacity of the eyes was observed in two animals found dead. This is seen in animals found dead as well as in those exposed to inhalation effects and the toxicologic significance of this finding is equivocal.
Other findings:
No data
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: other: Regulation EC on 1272/2008 (CLP)
Conclusions:
Under the conditions of this test, n-heptanoic acid induced mortality to rats receiving a single 4-hour maximum attainable exposure to 4.6 mg/l as an aerosol. Four of the ten rats died during the exposure, and therefore the LC50 was considered to be greater than 4.6 mg/l.
Executive summary:

In a single, four-hour, whole-body inhalation exposure (Bio/dynamics Inc., 1990), Sprague-Dawley rats (5/sex) were exposed to n-heptanoic acid. The test substance was administered into the breathing zone of the animals as an aerosol at a target concentration of 5.0 mg/l (limit test). All animals were held for a 14 -day post-exposure observation period and received daily detailed physical observations pretest through Day 15, and body weight measurements on Days 1, 2, 3, 5, 8 and 15. After the post-exposure period , all animals were sacrified and a complete gross postmortem examination was performed. The test animals received an average analytical exposure concentration, as determined gravimetrically, of 4.6 mg/l n-heptanoic acid with a nominal exposure concentration of 28 mg/l. Particle size distribution measurements showed an average mass median aerodynamic diameter of 3.8 microns with an average standard deviation of 2.0. Approximately three percent of the aerosol was one microns or less in size but 92 percent of the aerosol was 10 microns or less in size. These results indicated the test substance atmosphere was respirable in size to the rat. Four rats (two males and two females) were found dead upon removal of the animals from the chamber. All other animals survived the duration of the study. Observations noted during exposure included labored breathing, gasping, lacrimation, nasal discharge, matted coat and eye closure. Signs exhibited by surviving animals upon removal from the chamber and during the two hour post-exposure observation period on day 1 included laborated breathing and moist rales. Similar signs persisted for a few days after exposure and then all animals generally recovered. Significant weight losses were observed for a few days following exposure. Recovery of weight occurred over time and all surviving animals were in excess of their pre-exposure body weight by termination of the study. In conclusion, six of ten rats receiving a single four-hour maximum attainable exposure to 4.6 mg/l n-heptanoic acid as an aerosol, survived the exposure and subsequent 14 -day post-exposure observation period. However, four of the ten animals died during the exposure, and therefore the LC50 was considered to be greater than 4.6 mg/l. Moreover, signs of irritation were noted during the exposure and for several days after the exposure before the animals recovered.

Additional information

Acute oral and dermal toxicities: Due to a corrosive property of heptanoic acid, it was not necessary to conduct an acute oral and dermal studies.

Acute inhalation toxicity: In a single, four-hour, whole-body inhalation exposure, Sprague-Dawley rats (5/sex) were exposed to n-heptanoic acid. The test substance was administered into the breathing zone of the animals as an aerosol at a target concentration of 5.0 mg/l (limit test). All animals were held for a 14 -day post-exposure observation period and received daily detailed physical observations pretest through Day 15, and body weight measurements on Days 1, 2, 3, 5, 8 and 15. After the post-exposure period , all animals were sacrified and a complete gross postmortem examination was performed. The test animals received an average analytical exposure concentration, as determined gravimetrically, of 4.6 mg/l n-heptanoic acid with a nominal exposure concentration of 28 mg/l. Particle size distribution measurements showed an average mass median aerodynamic diameter of 3.8 microns with an average standard deviation of 2.0. Approximately three percent of the aerosol was one microns or less in size but 92 percent of the aerosol was 10 microns or less in size. These results indicated the test substance atmosphere was respirable in size to the rat. Four rats (two males and two females) were found dead upon removal of the animals from the chamber. All other animals survived the duration of the study. Observations noted during exposure included labored breathing, gasping, lacrimation, nasal discharge, matted coat and eye closure. Signs exhibited by surviving animals upon removal from the chamber and during the two hour post-exposure observation period on day 1 included laborated breathing and moist rales. Similar signs persisted for a few days after exposure and then all animals generally recovered. Significant weight losses were observed for a few days following exposure. Recovery of weight occurred over time and all surviving animals were in excess of their pre-exposure body weight by termination of the study. In conclusion, six of ten rats receiving a single four-hour maximum attainable exposure to 4.6 mg/l n-heptanoic acid as an aerosol, survived the exposure and subsequent 14 -day post-exposure observation period. However, four of the ten animals died during the exposure, and therefore the LC50 was considered to be greater than 4.6 mg/l. Moreover, signs of irritation were noted during the exposure and for several days after the exposure before the animals recovered.

Justification for classification or non-classification

Acute inhalation: harmful (LC50 > 4.6 mg/l; 4/10 animals died at this dose level)

Based on these data, heptanoic acid was classified category 4 for acute inhalation according to EU regulation (EC) No 1272/2008 (CLP), respectively.