Trichloroacetaldehyde

Endpoint summary

Description of key information

Repeated dose toxicity: Oral

A short-term toxicity study by the oral route does not need to be conducted because an appropriate inhalation study is available and inhalation is the most appropriate route of administration as based on the provided thorough and rigorous exposure assessment.

Repeated dose toxicity: Inhalation

The Low observed adverse effect concentration (LOAEC) for chloral is found to be 0.08 mg/L when exposed to male albino rats of Sprague Dawley strain for 14 days.

Repeated dose toxicity: Dermal

A short-term toxicity study does not need to be conducted because exposure of humans via dermal in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment. Also, the acute dermal toxicity value for test chemical (as provided in section 7.2.3) is >2000 mg/kg body weight. Given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that test chemical shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that test chemical shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

Key value for chemical safety assessment

Toxic effect type:

dose-dependent

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

a short-term toxicity study by the oral route does not need to be conducted because an appropriate inhalation study is available and inhalation is the most appropriate route of administration as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from NTRL report.

Qualifier:

according to guideline

Guideline:

other: Refer below principle

Principles of method if other than guideline:

2 weeks repeated dose toxicity study was performed using rats for the test compoun chloral upon repeated exposure by inhalation route

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Remarks:

Albino

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ARS/ Sprague Dawley, Madison, Wisconsin
- Females (if applicable) nulliparous and non-pregnant: Not applicable
- Age at study initiation: Young rats were used for the study
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: In stock cages
- Diet (e.g. ad libitum): Standard laboratory diet (Purina rat chow, Ralston Purina Co., St. Louis, Missouri) ad libitum
- Water (e.g. ad libitum): Water ad libitum
- Acclimation period: 5 days

DETAILS OF FOOD AND WATER QUALITY:
Food quality: Standard laboratory diet (Purina rat chow, Ralston Purina Co., St. Louis, Missouri) ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data

IN-LIFE DATES: From: To: Nov 06, 1972 - Nov 17, 1972

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 700L Plexiglas inhalation chamber
- Method of holding animals in test chamber: No data available
- Source and rate of air: Sources: Clean dry air (-40 C dewpoint); Rate of air: No data available
- Method of conditioning air: No data available
- System of generating particulates/aerosols: baffle plates were used
- Temperature, humidity, pressure in air chamber: 29.92 inches Hg pressure and 25 degree C temperature.
- Air flow rate: 0.13 L/min
- Air change rate: No data
- Method of particle size determination: No data available
- Treatment of exhaust air: No data available

TEST ATMOSPHERE
- Brief description of analytical method used: Air flow rate was measured using rotameter connected upstream of generator. The large air flow rate was measured by a hot wire anemometer
- Samples taken from breathing zone: No data available

VEHICLE (if applicable)
- Justification for use and choice of vehicle: Clean dry air
- Composition of vehicle: No data available
- Type and concentration of dispersant aid (if powder): No data available
- Concentration of test material in vehicle: 0 or 0.08 mg/L
- Lot/batch no. of vehicle (if required): No data available
- Purity of vehicle: No data available

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Air flow rate was measured using rotameter connected upstream of generator. The large air flow rate was measured by a hot wire anemometer

Duration of treatment / exposure:

Duration of treatment: 2 weeks (14 days) and 14 days recovery period
No. of exposure: 10 (During the 14 days treatment period)

Frequency of treatment:

4 hrs/day, 5 days/week

Remarks:

0 or 0.08 mg/L air

No. of animals per sex per dose:

Total: 20
0 mg/L air: 10 male rats
0.08 mg/L air: 10 male rats

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: No data
- Rationale for animal assignment (if not random): No data
- Rationale for selecting satellite groups: No data
- Post-exposure recovery period in satellite groups: 2 weeks
- Section schedule rationale (if not random): No data

Positive control:

No data

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. The animals were observed for mortality

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: During the experiment and after for any reactions displayed

BODY WEIGHT: Yes
- Time schedule for examinations: On first day and weekly thereafter

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available

OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available

HAEMATOLOGY: No data available
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available

CLINICAL CHEMISTRY: No data available
- Time schedule for collection of blood:
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available

URINALYSIS: No data available
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined. No data available

NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available

OTHER:

Sacrifice and pathology:

GROSS PATHOLOGY: Yes, five rats from each group of animals were sacrificed within a few hours of last inhalation exposure. The remaining animals were sacrificed after 2 week recovery period. Weight of liver, kidenys, spleen, heart, gonads, brain, lungs, thyroid glands and adrenal glands were determined for control and test animals.

HISTOPATHOLOGY: Yes, for microscopic observations, a complete set of tissues and organs were removed and preserved in 10% buffered formalin solution (pH 7.0). Histopathology was performed on adrenal glands, brain, gonads, heart, kidenys, lliver, lung, lymphnodes (cervical, peribronchial, mesentric), spleen, trachea and thyroid gland.

Statistics:

Analysis of variance and t tests were conducted on the absolute organ weights and on the organ to body weight and organ to brain weight ratios

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Sneezing was observed after 30 minutes. After 60 min, all animals exhibited ptosis and after 90 min few animals showed dyspnea. All these reactions continued with progressive increases in severity with each daily exposures to the chloral vapours until death or extreme weakness ocurred. Normal behaviour was exhibited by the three surviving rats after the last inhalation exposure.

Mortality:

mortality observed, treatment-related

Description (incidence):

One test animal died after sixth inhalation exposure, the second death occured during the seventh day. 4 animals at tenth inhalation exposure, 1 was necropsied to ensure one set of fresh tissues for accurate histological examination and three rats were survived two week of test period followed by two week of recovery period.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Body weight of treated animals was lower than the control animals. The three surviving rats gained a considerable amount of weight during the two week observation period but their final weght was still lower than that of the control rats.

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Most of the organ weight effects were observed due to starvation and were observed in lungs, brain, adrenal glands, gonads, heart, kidneys, liver and spleen. Significant difference was observed in organ weight and organ weight rations in the lungs and adrenal glands of only animals which was sacrificed after the two week of observation.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

A general stunting of growth of all organs of test rats which diied during the test period and those which were sacrificed after the 2 week observation period. Severe edema and severe diffuse red discoloration of the lungs in all the died rats. In treated animal on necropsy no food was found in the gastrointestinal tract. In two week recovery period animals, only white foci on the lungs of each animal was observed. No gross pathology findings were observed in the tissues and organs examined during the interim or final sacrifice.

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

No changes were attributed by exposure of chemical; all the effects were observed by naturally occurring disease or the method of sacrifice.

Histopathological findings: neoplastic:

not specified

Other effects:

not specified

Dose descriptor:

LOAEC

Effect level:

0.08 mg/L air

Based on:

test mat.

Sex:

male

Basis for effect level:

body weight and weight gain

clinical signs

gross pathology

histopathology: non-neoplastic

mortality

organ weights and organ / body weight ratios

Critical effects observed:

yes

Lowest effective dose / conc.:

0.08 mg/L air

System:

other: respiratory system

Organ:

adrenal glands

lungs

Treatment related:

yes

Dose response relationship:

not specified

Relevant for humans:

not specified

Table: 1 Individual body weight and weight gain data

Group	Individual body weight (g) Week no:					Two week body weight gain data	Four week body weight gain data
	0	1	2	3	Final
Untreated control	150	209	243	-	-	95	-
	166	224	258	-	-	92	-
	176	234	263	-	-	87	-
	150	215	199	-	-	49	-
	170	228	256	-	-	86	-
	153	98	156	195	257	3	104
	169	207	255	290	311	86	142
	165	225	258	280	310	93	145
	155	218	250	282	306	95	151
	164	240	269	304	335	105	171
Test	198	151	137	209	268	-31	100
	158	155	143	183	255	-15	97
	176	144	119	-	-	-57	-
	184	142	-	-	-	-	-
	168	147	119	-	-	-49	-
	162	177	141	-	-	-21	-
	168	178	152	208	262	-16	94
	167	150	134	-	-	-33	-
	174	156	113	-	-	-61	-
	170	155	-	-	-	-	-

 

Table: 2 Mean organ weight and ratio data

Organ: Lungs

Group	Absolute organ weight (g)	Organ/Body weight ratio (g/100g)	Organ/brain weight ration (g/g)
Interim control	1.307	0.538	0.815
Interim test	3.039**	2.520**	1.970**
Final control	1.537	0.505	0.900
Final test	1.980	0.774*	1.175*

* Statistically significant difference at the 95% CI level

** Statistically significant difference at the 99% CI level

 

Organ: Thyroid

Group	Absolute organ weight (g)	Organ/Body weight ratio (g/100g)	Organ/brain weight ration (g/g)
Interim control	0.018	0.008	0.012
Interim test	0.012	0.011	0.008
Final control	0.019	0.006	0.011
Final test	0.018	0.007	0.011

 

Organ: Spleen

Group	Absolute organ weight (g)	Organ/Body weight ratio (g/100g)	Organ/brain weight ration (g/g)
Interim control	0.692	0.282	0.431
Interim test	0.194**	0.160**	0.128**
Final control	0.721	0.238	0.425
Final test	1.184	0.446	0.702

** Statistically significant difference at the 99% CI level

Organ: Liver

Group	Absolute organ weight (g)	Organ/Body weight ratio (g/100g)	Organ/brain weight ration (g/g)
Interim control	0.983	3.929	6.023
Interim test	4.699**	3.908	3.083**
Final control	11.465	3.778	6.752
Final test	10.100	3.889	5.992

** Statistically significant difference at the 99% CI level

Organ: Kidneys

Group	Absolute organ weight (g)	Organ/Body weight ratio (g/100g)	Organ/brain weight ration (g/g)
Interim control	1.985	0.816	1.237
Interim test	1.164**	0.978**	0.770**
Final control	2.319	0.757	1.368
Final test	1.930	0.748	1.145

** Statistically significant difference at the 99% CI level

Organ: Heart

Group	Absolute organ weight (g)	Organ/Body weight ratio (g/100g)	Organ/brain weight ration (g/g)
Interim control	0.811	0.334	0.506
Interim test	0.524**	0.439**	0.346**
Final control	1.045	0.343	0.617
Final test	0.930	0.361	0.552

** Statistically significant difference at the 99% CI level

Organ: Gonads

Group	Absolute organ weight (g)	Organ/Body weight ratio (g/100g)	Organ/brain weight ration (g/g)
Interim control	3.981	1.646	2.485
Interim test	2.127**	1.774	1.402**
Final control	4.435	1.448	2.560
Final test	3.545	1.372	2.103

** Statistically significant difference at the 99% CI level

Organ: Adrenal glands

Group	Absolute organ weight (g)	Organ/Body weight ratio (g/100g)	Organ/brain weight ration (g/g)
Interim control	0.048	0.020	0.031
Interim test	0.056	0.047**	0.037
Final control	0.048	0.016	0.029
Final test	0.057*	0.022*	0.034

* Statistically significant difference at the 95% CI level

** Statistically significant difference at the 99% CI level

Organ: Brain

Group	Absolute organ weight (g)	Organ/Body weight ratio (g/100g)
Interim control	1.603	0.664
Interim test	1.514	1.269**
Final control	1.703	0.561
Final test	1.684	0.655

** Statistically significant difference at the 99% CI level

Conclusions:

The Low observed adverse effect concentration (LOAEC) for chloral is found to be 0.08 mg/L when exposed to male albino rats of Sprague Dawley strain for 14 days.

Executive summary:

2 weeks repeated dose toxicity study was performed using rats for the test compound chloral upon repeated exposure by inhalation route. The test compound was exposed to vapors of chloral at dose levels of 0 or 0.08 mg/L air to 20 male albino rats of Sprague Dawley strain. Inhalation exposure was were 4 hrs/day, 5 days/week for two week period. The animal were observed for mortality, any reactions displayed and body weight changes. Half of the rats from each group were sacrificed within a few hours after last inhalation exposure and the remaining half were sacrificed after two weeks recovery period. The animals were subjected to gross and histopathology and organ weights were recorded and subjected to statistical analysis. Six rats died during the two week exposure period and body weight losses were observed in all surviving animals. The animals showed untoward behavioral signs including sneezing, ptosis, dyspnea and weakness. The rats that died during the 2 weeks treatment period displayed severe edema and severe diffuse red discoloration of the lungs. Animals also exhibited reduced organ sizes and empty gastrointestinal tract. Animals surviving the 2 week treatment period and 2 week recovery period displayed white foci on lungs with no occurrences on red discoloration. No treatment related histopathological observation could be observed during the study. Statistical analyses of organ weights revealed several differences between control and treated animals. Lungs, spleen, liver, kidneys, heart and gonads were affected during chloral treatment. On the basis of observation made, the low observed adverse effect concentration (LOAEC) for chloral is found to be 0.08 mg/L when exposed to male albino rats of Sprague Dawley strain for 14 days.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEC

80 mg/m³

Study duration:

subacute

Experimental exposure time per week (hours/week):

4

Species:

rat

Quality of whole database:

Data is from NTRL report.

Organ:

adrenal glands

lungs

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

a short-term toxicity study does not need to be conducted because exposure of humans via the dermal route in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

Waiver

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity: Oral

A short-term toxicity study by the oral route does not need to be conducted because an appropriate inhalation study is available and inhalation is the most appropriate route of administration as based on the provided thorough and rigorous exposure assessment.

 

Repeated dose toxicity: Inhalation

2 weeks repeated dose toxicity study was performed using rats for the test compound chloral upon repeated exposure by inhalation route. The test compound was exposed to vapors of chloral at dose levels of 0 or 0.08 mg/L air to 20 male albino rats of Sprague Dawley strain. Inhalation exposure was were 4 hrs/day, 5 days/week for two week period. The animal were observed for mortality, any reactions displayed and body weight changes. Half of the rats from each group were sacrificed within a few hours after last inhalation exposure and the remaining half were sacrificed after two weeks recovery period. The animals were subjected to gross and histopathology and organ weights were recorded and subjected to statistical analysis. Six rats died during the two week exposure period and body weight losses were observed in all surviving animals. The animals showed untoward behavioral signs including sneezing, ptosis, dyspnea and weakness. The rats that died during the 2 weeks treatment period displayed severe edema and severe diffuse red discoloration of the lungs. Animals also exhibited reduced organ sizes and empty gastrointestinal tract. Animals surviving the 2 week treatment period and 2 week recovery period displayed white foci on lungs with no occurrences on red discoloration. No treatment related histopathological observation could be observed during the study. Statistical analyses of organ weights revealed several differences between control and treated animals. Lungs, spleen, liver, kidneys, heart and gonads were affected during chloral treatment. On the basis of observation made, the low observed adverse effect concentration (LOAEC) for chloral is found to be 0.08 mg/L when exposed to male albino rats of Sprague Dawley strain for 14 days.

 

Repeated dose toxicity: Dermal

A short-term toxicity study does not need to be conducted because exposure of humans via dermal in production and/or use is not likely as based on the provided thorough and rigorous exposure assessment. Also, the acute dermal toxicity value for test chemical (as provided in section 7.2.3) is >2000 mg/kg body weight. Given the use of the chemical; repeated exposure by the dermal route is unlikely since the use of gloves is common practice in industries. Thus, it is expected that test chemical shall not exhibit 28 day repeated dose toxicity by the dermal route. In addition, there is no data available that suggests that test chemical shall exhibit repeated dose toxicity by the dermal route. Hence this end point was considered for waiver.

 

 

Justification for classification or non-classification

Based on the data available, the given test chemical exhibit toxic nature upon repeated exposure by inhalation route of exposure. Hence, it is likely to classify in 'STOT RE 2' as per the criteria mentioned in CLP regulation. For repeated oral and repeated dermal toxicity waiver was added so, not possible to classify.