(1Z)-1-Chloro-2,3,3-trifluoroprop-1-ene

Endpoint summary

Description of key information

There are three repeated-dose toxicity studies for HCFO-1233yd(Z) – two via the inhalation route using substance vapours, and one via the oral route in which the test substance was administered by gavage.

In the 28-day oral toxicity study, male animals at the top dose (1000 mg/kg bw/day) exhibited effects in motor activity and forelimb grip strength.

In the 90-day inhalation toxicity study, changes in body weights were observed but these were reversible and did not alter the histology of these organs.

In the 14-day inhalation toxicity study, drowsiness and ataxic gait were observed in the highest dose (equivalent to 54.76 mg/L). Additional effects on organ weights were also noted.

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

Type of information:

experimental study

Adequacy of study:

key study

Study period:

12/01/2016 - 14/04/2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Route of administration:

oral: gavage

Details on oral exposure:

Dose levels:

0 (control), 40, 200, and 1000 mg/kg/day

Reason for dose selection:

In the dose range-finding study in which the test article dissolved in corn oil was administered by oral gavage at 40, 200, and 1000 mg/kg/day to 3 male and 3 female SD rats repeatedly for 7 days, no test article-related changes were noted at any dose in this study, therefore, 1000 mg/kg was selected as the high dose, and 200 and 40 mg/kg were selected as the middle and low doses, respectively, with a common ratio of 5. Recovery groups were set for the control and high dose groups to investigate the reversibility during 14-day withdrawal following 28-day administration.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Analytical method - Gas chromatograph
Column - DB-1301
Injection temp - 240°C
Detection temp. - 250°C
Column condition - Initial 40°C (10min hold), Rate lO°C/min, Final 240°C 15min

Frequency of treatment:

Once daily for 28 days

Dose / conc.:

40 mg/kg bw/day (nominal)

Dose / conc.:

200 mg/kg bw/day (nominal)

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

6

Control animals:

yes, concurrent no treatment

Observations and examinations performed and frequency:

The first day of administration was designated as Administration Day 1 (Day 1 ), and the day after Administration Day 28 as Recovery Day 1, and the day of necropsy was the day after Administration Day 28 (Day 29) or the day after Recovery Day 14 (Recovery Day 15). Administration Days 1 to 7 were designated as Administration Week 1, and subsequent days were counted on a 7 day-basis as follows: Administration Days 22 to 28 was Administration Week 4 (final week of administration), Recovery Days 1 to 7 was Recovery Week 1, and Recovery Days 8 to 14 was Recovery Week 2 (final week of recovery).

Sacrifice and pathology:

Animals were observed for external appearance, and blood was collected from the abdominal aorta under anesthesia with pentobarbital sodium. Animals were then euthanized by exsanguination and all organs and tissues were macroscopically observed. The organs and tissues described below were fixed and preserved in 10% neutral buffered formalin. The eyeballs and harderian glands were fixed and preserved in Davidson's fixative. The testes and epididymides were fixed in Bouin's solution and preserved in 70% ethanol. The lung was immersed in the fixative after infusing fixative into it. For bilateral organs, both sides of them were fixed and preserved.

Statistics:

Statistical analyses were performed using the computer system (MiTOX). The data during administration period obtained from the toxicity study groups and those from the recovery study groups were summed for statistical analyses.

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Clinical signs:

Malocclusion that was likely attributable to an accident in the cage in 1 female in the control group. During recovery period, no abnormalities were noted in clinical observation in males or females in any treated group.

Detailed clinical observation

During administration and recovery periods, no significant differences were noted in any parameters in males or females in any treated group compared with the control group.

Functional observations

During Administration Week 4, motor activity (30-40, 40-50, and 50-60 min) and grip strength of the forelimbs of males in the 1000 mg/kg group were significantly
lower than those in the control group. No significant differences were noted in any parameters in males or females in the 40 or 200 mg/kg group. During Recovery Week 2, motor activity (0-10, 10-20, 30-40, and 0-60 min) of females in the 1000 mg/kg group was significantly high. This change was not noted during Administration Week 4, and was considered unrelated to the test article administration. No significant differences were noted in motor activity in males or sensory and motor reactivity to stimuli or grip strength of males or females compared with the control group.

Mortality:

mortality observed, non-treatment-related

Description (incidence):

During administration period, 1 male (animal No. 10301) in the 200 mg/kg group was found dead before dosing on Administration Day 20.

Body weight and weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

No significant differences were noted in body weight or body weight gain during administration period in males or females in any treated group compared with the control group. During recovery period, body weight gain in females in the 1000 mg/kg group was significantly low. This was considered toxicologically insignificant because no significant differences were noted in body weight. In males, no significant differences were noted compared with the control group.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

There were no significant differences in food consumption during administration or recovery period in males or females in any treated group compared with the control group.

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, non-treatment-related

Description (incidence and severity):

In the toxicity study groups (at the end of administration), no significant differences were noted in any parameter in males or females in any treated group compared with the control group. In the recovery study groups (at the end of recovery), WBC and lymphocyte were significantly low in males and PT was significantly shortened in females in the 1000 mg/kg group. These changes were not noted at the end of administration and are considered toxicologically insignificant.

Clinical biochemistry findings:

effects observed, non-treatment-related

Description (incidence and severity):

In the toxicity study groups ( at the end of administration), T-Bil in males in the 40 and 1000 mg/kg groups was significantly lower than that in the control group; however, individual values were within the range of historical control data (mean 0.049 mg/dL, range 0.029 to 0.069 mg/dL). Since the low values have little clinical significance, this change was considered toxicologically insignificant. TG in males 2) in the 200 mg/kg group was significantly low, which was considered unrelated to the test article administration because no dose relationship was noted. No significant difference was noted in any parameter in females compared with the control group. In the recovery study groups, TG was significantly low and IP was significantly high in females in the 1000 mg/kg group. These changes were not noted at the end of administration and individual values were within the ranges of historical control data" (TG, mean 13.2 mg/dL, range 2.2 to 24.2 mg/dL; IP, mean 7.51 mg/dL, range 5.35 to 9.67 mg/dL) or slightly deviated from the ranges; therefore, these changes were considered toxicologically insignificant. In males, no significant differences were noted in any parameter compared with the control group.

Urinalysis findings:

no effects observed

Description (incidence and severity):

There were no significant differences in any parameters during Administration Week 4 or Recovery Week 2 in males or females in any treated group compared with the control group.

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, non-treatment-related

Description (incidence and severity):

In the recovery study groups, absolute testis weight and relative prostate weight were significantly low in males and relative adrenal weight was significantly high in females in the 1000 mg/kg group. These changes were considered toxicologically insignificant because no changes related to the test article administration were noted in the weight or histopathology of these organs at the end of administration, and individual values were within the ranges of historical control data
(testis, mean 3.108 g, range 2.542 to 3.674 g; prostate, mean 145.993 mg/100 g, range 81.573 to 210.413 mg/100 g; adrenal, females, mean 31.336 mg/100 g, range 21.130 to 41.542 mg/100 g).

Gross pathological findings:

effects observed, non-treatment-related

Description (incidence and severity):

Necropsy at the end of administration in the toxicity study groups revealed dilatation of the renal pelvis in 1 male and malocclusion in 1 female in the control group.
Other than these, no abnormalities were noted in any animal. The male that died in the 200 mg/kg group (animal No. 10301) showed no abnormalities. Necropsy in the recovery study groups revealed no abnormalities in males or females in any treated groups.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

In the toxicity study groups, histopathological findings including microgranuloma in the liver and basophilic change of the renal tubule in the kidneys were sporadically noted in males or females in the 1000 mg/kg group. These changes were noted also in the control group or historical control data", and of low frequency; therefore, these were determined to be incidental findings. The male that died in the 200 mg/kg group (animal No. 10301) showed slight alveolar and perivascular edema in the lung.

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Key result

Dose descriptor:

NOAEL

Effect level:

200 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

behaviour (functional findings)

Critical effects observed:

no

Conclusions:

A repeated dose oral toxicity study was conducted in which HCFO-1233yd(Z) was administered to 6 males and 6 females per group of Crl:CD (SD) rats by oral gavage at 0 (control: com oil), 40, 200, and 1000 mg/kg once daily for 28 days. Recovery study groups at doses of 0 and 1000 mg/kg were separately employed, and during the 14-day withdrawal period following the end of 28-day administration, reversibility of the toxicity that occurred was investigated in 6 males and 6 females per group.

In the 40 mg/kg group, no changes related to the test article administration were noted in clinical observation, body weight, food consumption, detailed clinical observation, functional observations, urinalysis, hematology, biochemistry, necropsy, or organ weight in males or females.

In the 200 mg/kg group, 1 male died on Administration Day 20. Histopathological examination of this animal revealed slight alveolar and perivascular edemas in the lung, which indicated circulatory disorder. This was considered unrelated to the test article administration because this change was not noted in the 1000 mg/kg group. No effects of the test article administration were noted in any of the other parameters in males or females.

In the 1000 mg/kg group, motor activity and grip strength of the forelimbs were significantly low during Administration Week 4 in males. In the acute toxicity study of HCFO-1233yd(Z), staggering gait was noted at 2000 mg/kg; therefore, the changes noted in the present study were considered related to the test article administration. This change was not noted during the 2 recovery weeks, indicating reversibility of the change. There were no changes related to the test article administration in males or females in any other examination parameters including histopathology.

As described above, administration of 1000 mg/kg HCFO-1233yd(Z) resulted in decreases in motor activity and grip strength of the forelimbs in males. While in females, no toxic changes related to the test article administration were noted in clinical observation, detailed clinical observation, functional observations, body weight, food consumption, urinalysis, hematology, biochemistry, necropsy, organ weight, or histopathology at doses up to 1000 mg/kg.

Executive summary:

On the basis of these results, the No-Observed Adverse Effect Level (NOAEL) of HCFO-1233yd(Z) was determined to be 200 mg/kg/day for males and 1000 mg/kg/day for females under the present study conditions.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

System:

central nervous system

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

Study period:

26/08/2016 - 24/10/2016

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Route of administration:

inhalation: vapour

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

The rats held in the restraint tubes were connected to the chamber to start exposure after supplying the test atmosphere to the chamber. The rats were dismounted from the chamber to terminate exposure 6 hours after the start of exposure.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

GC: GC-14B (Shimadzu Corp.)
Recorder: D-7500 (Hitachi, Ltd., Tokyo, Japan)
Syringe: Micro syringe (10 and 100 μL: Hamilton Company, NV, USA) 1 mL gastight syringe (#1001: Hamilton Company)
Sampling bag: 1.56 L of inner volume (actual inner volume, Smart bag: GL Sciences Inc., Tokyo, Japan)

Duration of treatment / exposure:

6 hours

Frequency of treatment:

5 times a week for 2 weeks

Dose / conc.:

2 500 ppm (nominal)

Dose / conc.:

13.56 mg/L air (analytical)

Dose / conc.:

5 000 ppm (nominal)

Dose / conc.:

26.95 mg/L air (analytical)

Dose / conc.:

10 000 ppm (nominal)

Dose / conc.:

54.76 mg/L air (analytical)

No. of animals per sex per dose:

6

Control animals:

yes, concurrent no treatment

Observations and examinations performed and frequency:

Daily observation was conducted from the first day of exposure to the day of necropsy.
The observation frequency was shown below:
Exposure day: twice a day (before and after exposure)
Other day: once a day

Sacrifice and pathology:

All animals were subjected to necropsy on day 15.
The animals were subjected to necropsy after the euthanisation by exsanguination from the abdominal aorta after blood collection.

Statistics:

Initially, variance was assessed using Bartlett's test (significance level: 5%). When the
variance was homogeneous, multiple comparison test was conducted using Dunnett's
method. When the variance was heterogeneous, multiple comparison test was
conducted using Steel test. The multiple comparison tests were conducted by two-tailed
test with significance level of 1% and 5%.
The numerical data obtained from the animals subjected to the recovery period, variance
was assessed using F test (significance level: 5%). When the variance was
homogeneous, group difference comparison test was conducted using t-test, otherwise
Aspin-Welch test was applied (two-tailed test, significance level: 1% and 5%).

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

In the 10,000 ppm group, drowsiness and ataxic gait were observed in males and females at observation after exposure. Moreover, rale was sporadically observed in females of this group after exposure.

Mortality:

mortality observed, treatment-related

Description (incidence):

On day 7, one female of the HCFO-1233yd(Z) 10000 ppm group died after exposure.

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Statistically significant lower body weights were noted in males of the HCFO-1233yd(Z) 10000 ppm group on each measurement day on and after day 4 in comparison with those of the control group.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

effects observed, non-treatment-related

Description (incidence and severity):

There were no remarkable changes in the ophthalmological findings from the pre-exposure period to the exposure period. Several spontaneous findings were noted in a few animals including the control group.

Haematological findings:

effects observed, non-treatment-related

Description (incidence and severity):

Males of the HCFO-1233yd(Z) 5000 and 10000 ppm groups indicated statistically significant lower values of WBC and lymphocytes count in comparison with those of the control group.

Clinical biochemistry findings:

effects observed, non-treatment-related

Description (incidence and severity):

Males of the HCFO-1233yd(Z) 10000 ppm group indicated statistically significant lower value of ALP in comparison with that of the control group. Females of the HCFO1233yd(Z) 10000 ppm group indicated higher value of ALAT and lower value of ALP. The low value of ALP does not have toxicological significance.

As no exposure concentration dependent change, lower value of ASAT was noted in females of the HCFO-1233yd(Z) 5000 ppm group. This change was considered to be incidental.

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Males of the HCFO-1233yd(Z) 10000 ppm group had statistically significant higher value of the body weight-relative liver weight and lower value of the absolute spleen weight in comparison with those of the control group. In females, the HCFO-1233yd(Z) 5000 ppm group had a higher value of the body weight-relative liver weight, the HCFO-1233yd(Z) 10000 ppm group had higher values of the absolute and body weight-relative liver weights, and lower value of the body weight-relative spleen weight.

Gross pathological findings:

effects observed, non-treatment-related

Description (incidence and severity):

Edema of the lungs was observed in female of the HCFO-1233yd(Z) 10000 ppm group, which died after exposure.

No abnormalities attributable to the test substance were noted in males or females in the animals subjected to the necropsy after the exposure period. Unilateral small testis was found in one male of the HCFO-1233yd(Z) 2500 ppm group. Since this finding did not have exposure concentration dependency, it was considered to incidental change.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not examined

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Key result

Dose descriptor:

NOAEC

Effect level:

26.95 mg/L air (analytical)

Based on:

test mat.

Sex:

male

Basis for effect level:

organ weights and organ / body weight ratios

Key result

Dose descriptor:

NOAEC

Effect level:

13.56 mg/L air (analytical)

Based on:

test mat.

Sex:

female

Basis for effect level:

organ weights and organ / body weight ratios

Critical effects observed:

no

Conclusions:

Subacute inhalation toxicity of HCFO-1233yd(Z) in rats was evaluated by repeated 14-day inhalation exposure.

The actual exposure concentrations were 2540 ppm (13.56 mg/L), 5050 ppm (26.95 mg/L), and 10260 ppm (54.76 mg/L) to the target exposure concentrations of 2500, 5000, and 10000 ppm, respectively.

In the HCFO-1233yd(Z) 10000 ppm group, one female died on day 7. Edema of the lungs was observed in this animal. When the test substance was exposed at 10000 ppm, drowsiness and ataxic gait were observed in males and females, rale was observed in females. Males indicated lower value of body weight. Higher value of ALAT was induced by the test substance exposure in females. In organ weight, higher value of the liver and lower value of the spleen were noted in males and females. In the HCFO-1233yd(Z) 5000 ppm group, there was higher value of the liver weight in females. Drowsiness and ataxic gait suggested that the test substance has anesthetic action.

Since the changes in WBC and lymphocytes count in the HCFO-1233yd(Z) 5000 and 10000 ppm groups indicated exposure concentration dependency, it was not able to rule out the possibility of attributable to the test substance in these changes. However, the observed values were within the background data of the test facility. Therefore, it was concluded that the changes in hematology were not adverse effects by the test substance.

Executive summary:

The test substance exposure at 54.76 mg/L resulted in the changes of clinical sign, body weight, blood chemistry, and organ weight.  Since, the similar change in organ weight was also noted in females exposed to 26.95 mg/L, it is concluded that no-observed-adverse effect-level of the test substance is 26.95 mg/L in males and 13.56 mg/L ppm in females as actual concentration in this study.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Species:

rat

System:

central nervous system

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Repeated-Dose Toxicity - Oral Route

A repeated dose oral toxicity study was conducted in which HCFO-1233yd(Z) was administered to 6 males and 6 females per group of Crl:CD (SD) rats by oral gavage at 0 (control: com oil), 40, 200, and 1000 mg/kg once daily for 28 days. Recovery study groups at doses of 0 and 1000 mg/kg were separately employed, and during the 14-day withdrawal period following the end of 28-day administration, reversibility of the toxicity that occurred was investigated in 6 males and 6 females per group.

In the 40 mg/kg group, no changes related to the test article administration were noted in clinical observation, body weight, food consumption, detailed clinical observation, functional observations, urinalysis, haematology, biochemistry, necropsy, or organ weight in males or females.

In the 200 mg/kg group, 1 male died on Administration Day 20. Histopathological examination of this animal revealed slight alveolar and perivascular edemas in the lung, which indicated circulatory disorder. This was considered unrelated to the test article administration because this change was not noted in the 1000 mg/kg group. No effects of the test article administration were noted in any of the other parameters in males or females.

In the 1000 mg/kg group, motor activity and grip strength of the forelimbs were significantly low during Administration Week 4 in males. In the acute toxicity study of HCFO-1233yd(Z), staggering gait was noted at 2000 mg/kg; therefore, the changes noted in the present study were considered related to the test article administration. This change was not noted during the 2 recovery weeks, indicating reversibility of the change. There were no changes related to the test article administration in males or females in any other examination parameters including histopathology.

As described above, administration of 1000 mg/kg HCFO-1233yd(Z) resulted in decreases in motor activity and grip strength of the forelimbs in males. While in females, no toxic changes related to the test article administration were noted in clinical observation, detailed clinical observation, functional observations, body weight, food consumption, urinalysis, haematology, biochemistry, necropsy, organ weight, or histopathology at doses up to 1000 mg/kg.

Repeated-Dose Toxicity - Inhalation Route

90 -Day Subchronic Study

Subchronic inhalation toxicity of HCFO-1233yd(Z) in rats was evaluated by repeated 90-day inhalation exposure followed by 2-week recovery period.

The actual exposure concentrations were 1270ppm (6.78 mg/L), 2550 ppm (13.61 mg/L), and 5080 ppm (27.11 mg/L) in the target exposure concentrations of 1250, 2500, and 5000 ppm, respectively.

In males of the highest dose group, the test substance exposure resulted in low values of body weight and food consumption during the exposure period, high values of body weight-relative ratios in the submandibular glands, liver, and adrenals at the end of the exposure period.  In females of the HCFO-1233yd(Z) group, high value of the liver weight was noted at the end of the exposure period.  Regarding low values of food consumption in females of the HCFO-1233yd(Z) 2500 and 5000 ppm groups, these were not accompanied with the changes in body weights.  Therefore, it was concluded that the changes in food consumption were not adverse effects by the test substance. No noteworthy changes were noted in those parameters during the recovery period, suggesting reversibility from the adverse effects.

Histopathological alterations after the exposure period in the HCFO-1233yd(Z) 5000ppm group were degeneration of ameloblasts in the maxillary incisor tooth, atrophy of the seminiferous tubules in the testis, cell debris and/or reduced sperm in the lumen in the epididymis.  After the recovery period, these changes showed reversibility. No histological changes were noted in the liver, submandibular glands, or adrenals. Therefore, the weight changes in the liver and submandibular glands were considered to be reactive change not accompanied by organic alterations. Regarding the adrenal weight, it is considered that the changes reflected the body weight differences.

No adverse effects by the test substance were noted in clinical observations, ophthalmological examinations, urinalysis, haematology, or blood chemistry in males or females.  

Urinary fluorine ion concentration indicated exposure concentration-dependent increase during the exposure period, and no clear difference between the control group and HCFO-1233yd(Z) 5000 ppm group during the recovery period. These results suggested that the test substance was excreted to urine and no bioaccumulation potentials.

14 -Day Subacute Study

Subacute inhalation toxicity of HCFO-1233yd(Z) in rats was evaluated by repeated 14-day inhalation exposure.

The actual exposure concentrations were 2540 ppm (13.56 mg/L), 5050 ppm (26.95 mg/L), and 10260 ppm (54.76 mg/L) to the target exposure concentrations of 2500, 5000, and 10000 ppm, respectively.

In the HCFO-1233yd(Z) 10000 ppm group, one female died on day 7.  Edema of the lungs was observed in this animal. When the test substance was exposed at 10000 ppm, drowsiness and ataxic gait were observed in males and females, rale was observed in females.  Males indicated lower value of body weight.  Higher value of ALAT was induced by the test substance exposure in females.  In organ weight, higher value of the liver and lower value of the spleen were noted in males and females.  In the HCFO-1233yd(Z) 5000 ppm group, there was higher value of the liver weight in females. Drowsiness and ataxic gait suggested that the test substance has anaesthetic action.

Since the changes in WBC and lymphocytes count in the HCFO-1233yd(Z) 5000 and 10000 ppm groups indicated exposure concentration dependency, it was not able to rule out the possibility of attributable to the test substance in these changes.  However, the observed values were within the background data of the test facility.  Therefore, it was concluded that the changes in haematology were not adverse effects by the test substance.

Justification for classification or non-classification

Based upon the results of the 14 -day inhalation toxicity, specifically the observation of ataxic gait and drowsiness, HCFO-1233yd(Z) will be classified for Specific Target Organ Toxicity - Single Exposure. As the concentrations tested are above those stated in the CLP guidance for SE 1 and SE 2, the substance is classified for STOT SE Category 3 (with associated hazard statement H336 - May cause drowsiness or dizziness).

HCFO-1233yd(Z) is classified for STOT Single Exposure Category 3 according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008 or UN Globally Harmonized System of Classification and Labelling of Chemicals (GHS).