Glycollic acid

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

; 3 minor deviations, insignificant. 4 of the rats, 3.8 mg/L, without gross evaluation at necropsy. No tissues from 2 male rats in the 5.2 mg/L available for microscopy. 0.60 mg/L animals in recovery for 15 days rather 14 days

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

yes

Remarks:

; 3 minor deviations, insignificant. 4 of the rats, 3.8 mg/L, without gross evaluation at necropsy. No tissues from 2 male rats in the 5.2 mg/L available for microscopy. 0.60 mg/L animals in recovery for 15 days rather 14 days

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Glycollic acid

EC Number:

201-180-5

EC Name:

Glycollic acid

Cas Number:

79-14-1

Molecular formula:

C2H4O3

IUPAC Name:

2-hydroxyacetic acid

Details on test material:

Glycolic acid 70% solution

Test animals

Species:

rat

Strain:

other: Crl:CD®(SD)IGS BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

Charles River Breeding Laboratories, Raleigh, North Carolina, USA

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

Rats were individually restrained in perforated stainless steel cylinders with conical nose pieces. The restrainers were inserted into the faceplate of the exposure chamber so that only the nose of each rat extended into the chamber. The chamber was a glass cylinder with a nominal internal volume of 34 L. The chamber airflow was set at approximately 12 air changes per hour. Airflow was monitored continually and recorded at 30 minute intervals. Chamber environmental conditions were monitored regularly through exposure.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric analysis at 30-45 min intervals during exposure

Duration of exposure:

4 h

Remarks on duration:

single exposure period

Concentrations:

0, 0.6, 2.1, 3.8 and 5.2 mg glycolic acid/L air.

Characterization of the chamber atmosphere during each exposure showed the mean total aerosol concentration to be 5.2, 3.8, 2.1 and 0.60 mg/L Glycolic Acid.

No. of animals per sex per dose:

TEST ANIMALS
- Source: Charles River Breeding Laboratories, Raleigh, North Carolina.
- Age at study initiation: Approximately 8 weeks old.
- Weight at study initiation: Males ranged from 237 g to 295 g, females ranged from 198 g to 202 g.
- Housing:Singly or in pairs (sexes separate) in suspended, stainless steel, wire mesh cages.
- Diet (e.g. ad libitum): PMI Nutrition International, Inc. Certified Rodent LabDiet 5002 ad libitum.
- Water (e.g. ad libitum): Tap water ad libitum.
- Acclimation period: Quarantined for 6 days prior to testing.
- Dosing: One group of 5 male and 5 female rats and three groups of 10 male rats. Additional satellite groups of 5 rats were tested for the four test concentrations. A control group of 10 rats was used. Additionally, four groups of 5 male rats per dose were used for a satellite experiment.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23+/-1°C.
- Humidity (%): 50 +/- 10%.
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark on a timer-controlled cycle

Control animals:

yes

Details on study design:

One group of 5 male and 5 female rats and 3 groups of 10 male rats each were exposed to an atmosphere of Glycolic Acid in air and allowed to recover for 14 or 15 days. These rats were designated for LC50 determination. The 0.60 mg/L group of rats was inadvertently kept for a 15-day recovery period. This deviation did not affect the results of the study. After the recovery period, all surviving rats were sacrificed for gross pathology evaluations. Male and female rats also underwent microscopic examination of the nose, larynx, pharynx, and lungs. Four groups of 5 male rats each were exposed along with the groups designated for LC50 determination. These rats were designated as satellite animals. All surviving satellite animals were sacrificed approximately 24 hours after exposure for microscopic examination of the nose, larynx, pharynx, and lungs. One group of 10 male rats was exposed to air only. These rats were designated as controls. Five control rats were sacrificed approximately 24 hours after exposure for microscopic examination of the nose, larynx, pharynx, and lungs. The remaining 5 rats were allowed to recover for 14 days, then received the same treatment as the control rats from the initial sacrifice. All rats were exposed nose-only for a single 4-hour period.

Statistics:

Finney, D.S. (1971). Probit analysis, Third Edition, Cambridge University Press, Cambridge.

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LC50

Effect level:

> 5.2 mg/L air

Exp. duration:

4 h

Remarks on result:

other: nose-only

Effect levels 2

Sex:

male

Dose descriptor:

LC50

Effect level:

3.6 mg/L air

95% CL:

2.4 - 8.9

Exp. duration:

4 h

Remarks on result:

other: nose-only

Mortality:

Exposure to 5.2 mg/L glycolic acid produced 60% mortality in male rats and no mortality in female rats. Subsequent exposures were made on male rats only. Mortality in male rats exposed to 0.6, 2.1 and 3.8 mg/L glycolic acid was 0, 20 and 60% respectively. Rats died either during exposure, or within 1 to 10 days following exposure to the test substance. Mortality was associated with ulcerative lesions founds in the larynges.

Clinical signs:

other: Observations for clinical signs commenced after removal of the rats from the restrainers. Signs of toxicity included gasping, lung noise, hunched posture, nasal and ocular discharge. Additional clinical signs noted later during the recovery period includ

Body weight:

All exposed rats showed body weight losses the day after exposure. One rat in the 5.2 mg/L treatment and all rats in the 3.8, 2.1 and 0.6 mg/L treatments experienced an overall weight gain during the recovery period, although some transient weight losses did occur.

Gross pathology:

No test substance associated target organ gross changes were observed in exposed male or female rats.

Microscopic changes, attributed to treatment induced tissue irritation, were observed in the noses, larynges and lungs of male rats and nose and larynges of female rats. Mild to severe laryngeal ulceration was present in all treated male groups and mild effects were present in the female group. There was not a clear dose response in regard to lesion severity at lower exposure levels, but exposure to 3.8 mg/L and above was associated with severe ulceration. Minimal to mild subacute/chronic inflammation was present in lungs of rats exposed to 2.1, 3.8 and 5.2 mg/L glycolic acid.

Other findings:

No further information.

Any other information on results incl. tables

Mortality

-No mortality was observed in male rats designated as satellite animals or in control rats.

-5.2 mg/L produced 60% mortality in male rats (3/5) and no mortality in females (0/5).

-Only male rats were used for subsequent exposures at concentrations less than 5.2 mg/L.

-Male rat mortality at the other exposure concentrations were 60% for 3.8 mg/L (6/10), 20% for 2.1 mg/L (2/10), and 0% for 0.60 mg/L (0/10).

 

Clinical signs

-Clinical signs were collected for LC50 rats, but not for satellite or control rats.

-Immediately following exposure, gasping, lung noise, hunched posture, nasal and ocular discharge were observed. Stained fur, wet fur and perinea were also observed, but attributed to the method of restraint.

-During recovery, gasping, lung noise, hunched posture, lethargy, ocular and nasal discharge, sore eyes, sore nose, sore chin, vocalization, alopecia and stained and/or wet fur and/or perinea were observed

 

Bodyweight

-Body weights were collected for LC50 rats, but not for satellite or control rats.

-All male rats and 4 of 5 female rats which survived the exposure to 5.2 mg L Glycolic Acid experienced slight to severe body-weight losses the day after exposure. Males lost 12-15% of pre-exposure body weight and females lost 0.1 to 5.1%. All male rats that survived the 3.8 mg/L exposure had losses that ranged from 6.5 to 16% of pre-exposure body weight. Rats from the 2.1 mg/L group showed losses that ranged from 2.4 to 14 % of pre-exposure body weight and rats from the 0.60 mg/L group exhibited losses that ranged from 0.3 to 14% of pre-exposure body weight. One rat in the 5.2 mg/L group and all rats in the 3.8, 2.1 or 0.60 mg/L groups experienced overall weight gain during the recovery period, though some transient weight losses did occur.

 

Pathology

No test substance-associated target organ gross changes were observed in exposed male or female rats designated for LC50 determination. Four male rats exposed to 3.8 mg/L did not receive gross evaluations due to inadvertent errors at necropsy.

 

Other findings

Microscopic Observations

- Test substance-associated microscopic changes, attributable to tissue irritation, were observed in noses, larynges and lungs of male rats and nose and larynges of female rats. Minimal to mild nasal lesions, seen in all treated groups, consisted of degeneration of respiratory and/or olfactory epithelium. In the respiratory region, changes were in the mucosa lining the dorsal, middle and ventral meatuses, and on the septum and turbinates of the anterior nose. The changes consisted of loss of columnar and/or transitional cells and denudation of mucosal epithelium or presence of degenerate acidophilic cells or basophilic regenerative cells, occasionally flattened to cover maximal surface area. In the olfactory region, changes were on the septum and ethmoid turbinates and ranged from segmental loss of neuroepithelial cells, the usual, to occasional loss of neuroepithelial and sustentacular cells, resulting in mucosal denudation. Regeneration was noted as basophilic, slightly disorganized hypercellular segments of olfactory mucosa.

-Mild to severe laryngeal ulceration was present in all treated male groups and mild effects were present in the female group. In most instances, sections of larynges were examined microscopically at the base of the epiglottis and ventral pouch region. There was not a clear dose response in regard to lesion severity at lower exposure levels, but exposure to 3.8 mg/L and above was associated with severe ulceration.

- Minimal to mild subacute/chronic inflammation was present in lungs of rats exposed to 2.1, 3.8, and 5.2 mg/L Glycolic Ac

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

For nose only exposure:
female 4 hour LC50 = >5.2 mg/L
male 4 hour LC50 = 3.6 mg/L (95% confidence limits of 2.4 – 8.9 mg/L).
Based on the microscopic pathology observations, the no-observed-effect level (NOEL) for a single 4-hour exposure to aerosols of glycolic acid in male and female rats was not established.

The purpose of this study was two-fold. The primary purpose was to determine a 4-hour inhalation LC50 for Glycolic Acid in male and female rats. The secondary purpose was to evaluate the potential of the test substance to induce lesions in the nose, pharynx, larynx and lungs following a single 4-hour inhalation exposure.

Under the conditions of this study, the 4-hour inhalation median lethal concentration (LC50) for Glycolic Acid in female rats was greater than 5.2 mg/L. The 4-hour LC50 for Glycolic Acid in male rats was 3.6 mg/L (95% confidence limits 2.4-8.9 mg/L). Based upon the microscopic pathology observations, the no-observed-effect level for a single 4-hour exposure to aerosols of Glycolic Acid in male and female rats was not established.

Executive summary:

For nose only exposure: female 4 hour LC50= >5.2 mg/L, male 4 hour LC50= 3.6 mg/L (95% confidence limits of 2.4 – 8.9 mg/L). Based on the microscopic pathology observations, the no-observed level (NOEL) for a single 4 -hour exposure to aerosols of glycolic acid in male and female rats was not established. Under the conditions of this study, Glycolic acid is considered harmful by inhalation.